ID Seminar, October, 12, 2001

1
Emergency discovery of novel antimicrobials
among known drugs in response to new and
re-emerging infectious threats A. Cherkasov UBC
/ VGH Infectious Diseases artc_at_interchange.ubc.ca
2

• Binary QSAR Models for Antibiotic-likeness
• and Metabolite-likeness
• 2. Finding potential antibiotics among common
• drugs, substances
• 3. Attacking essential proteins in emerging
• and re-emerging pathogens Prospectives,
  Protocols

3

• Binary QSAR Models for Antibiotic-likeness
• and Metabolite-likeness

4
QSAR quantitative structure-activity relationships
GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAA
TTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCT
GGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGG
GCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACAT
CTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGC
CCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAG
TGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTT
GCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTT
TGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGG
TTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGT
CTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCA
GGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTT
TATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAA
GCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTC
TGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATG
ATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGG
ATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGC
CCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGG
GAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACT
TTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCC
CATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGT
TTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTC
TGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAG
TAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAG
GGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTC
TCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGC
TGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCC
CAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAA
ACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG
GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGAT
CATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTT
CTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTG
ACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCA
GCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCC
AACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTA
GGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTG
CGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTT
CTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACC
CTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGG
AAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCC
TTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCA
CCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAG
TGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACAT
TTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACAT
ATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCA
GGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCA
CAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGC
CTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGA
GTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAA
GGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCC
AGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGA
GCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCA
TTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGG
GCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCC
TACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAG
TGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCT
GCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGG
CCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCAC
ATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACC
TGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCA
TTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTG
CCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGC
ACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGG
GTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATG
ACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACAC
AGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTA
AGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAG
GCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTT
CTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCT
GTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGT
CTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT
CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGC
TGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCA
AGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATG
TGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCT
CATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTT
GAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGC
AAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATG
GGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGA
GTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTC
TCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACC
TAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTT
GGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCC
CTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCA
GCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAG
GTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAG
GGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGA
TGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAA
CAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGT
CTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACA
GTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCC
AGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATT
TTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGG
CTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTC
GTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGG
AGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCG
CTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCG
TGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTG
GCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCG
AAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGG
AGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGAC
TCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGC
TCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCG
TGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGG
TGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCAC
TGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGC
TACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCA
TGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCA
CTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGA
AGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGG
CAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGT
CCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCC
CCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTG
TCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCT
GCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTT
CATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGA
CTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCA
CAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGC
TTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATT
CCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGG
GGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGT
CATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCC
AGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTT
GCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTC
TAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGG
AAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCA
GGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGC
TTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAA
GCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTT
CTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGA
GGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATT
CCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAA
ATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTG
ACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGN
GCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGG
GAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGAC
AGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGT
AGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTT
CCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGA
GGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCA
TGTTGAA
Molecular structure gets translated into
numbers (descriptors)
Mathematical function f ( Descriptors) Activity
THE UNIVERSITY OF BRITISH COLUMBIA MEDICINE
INFECTIOUS DISEASES
5
Inductive descriptors
GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAA
TTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCT
GGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGG
GCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACAT
CTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGC
CCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAG
TGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTT
GCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTT
TGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGG
TTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGT
CTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCA
GGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTT
TATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAA
GCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTC
TGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATG
ATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGG
ATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGC
CCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGG
GAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACT
TTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCC
CATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGT
TTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTC
TGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAG
TAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAG
GGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTC
TCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGC
TGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCC
CAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAA
ACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG
GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGAT
CATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTT
CTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTG
ACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCA
GCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCC
AACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTA
GGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTG
CGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTT
CTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACC
CTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGG
AAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCC
TTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCA
CCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAG
TGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACAT
TTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACAT
ATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCA
GGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCA
CAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGC
CTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGA
GTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAA
GGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCC
AGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGA
GCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCA
TTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGG
GCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCC
TACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAG
TGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCT
GCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGG
CCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCAC
ATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACC
TGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCA
TTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTG
CCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGC
ACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGG
GTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATG
ACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACAC
AGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTA
AGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAG
GCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTT
CTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCT
GTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGT
CTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT
CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGC
TGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCA
AGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATG
TGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCT
CATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTT
GAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGC
AAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATG
GGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGA
GTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTC
TCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACC
TAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTT
GGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCC
CTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCA
GCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAG
GTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAG
GGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGA
TGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAA
CAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGT
CTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACA
GTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCC
AGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATT
TTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGG
CTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTC
GTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGG
AGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCG
CTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCG
TGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTG
GCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCG
AAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGG
AGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGAC
TCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGC
TCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCG
TGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGG
TGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCAC
TGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGC
TACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCA
TGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCA
CTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGA
AGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGG
CAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGT
CCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCC
CCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTG
TCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCT
GCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTT
CATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGA
CTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCA
CAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGC
TTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATT
CCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGG
GGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGT
CATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCC
AGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTT
GCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTC
TAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGG
AAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCA
GGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGC
TTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAA
GCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTT
CTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGA
GGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATT
CCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAA
ATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTG
ACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGN
GCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGG
GAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGAC
AGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGT
AGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTT
CCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGA
GGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCA
TGTTGAA
The relative area of frontal Screening of a
surface of atom A by atom B (shown as a green
shadow) is
6
Inductive QSAR Descriptors
Average Electronegativities of the
Negatively/Positively Charged Atoms Molecular
(equalized) Electronegativity Total Formal
Charge Average Atomic Hardness Sum of Atomic
Hardnesses Average Negative/Positive
Charges Largest Positive Charge Average Atomic
Hardnesses of Negatively/Positively Charged
Atoms Hardness of the Most Positively Charged
Atom Largest Hardness among the
Negatively/Positively Charged Atoms Sum of
Softnesses of Negatively Charged Atoms Steric
Effect on the Most Negatively Charged Atom Most
Negative Inductive Constant of an Atom in
Molecule Largest Positive Inductive Effect on an
Atom in Molecule The Smallest Steric Effect on a
Atom in Molecule Sum of all Negative Inductive
Effects on Atoms in Molecule ..
7
QSAR models for antibiotics, drugs and bacteria
and human metabolites A. Cherkasov. J Chem Inf
Model, 46, 1214 (2006), E. Karakoc et al
Bioinformatics, 22, e243v (2006) QSAR models for
antimicrobial peptides A. Cherkasov. Current
Computer-Aided Drug Design, 1, 21 (2005) H.
Jenssen et al Chem Biol Drug Des. 70, 134
(2007) A hybrid QSAR/Docking approach
Progressive docking has been developed A.
Cherkasov et al, J Med Chem. 49, 7466
(2006) Various low-micromolar to nanomolar
inhibitors developed with the help of inductive
QSAR solutions A. Cherkasov et al, J Med Chem,
48, 3203 (2005) A. Cherkasov et al J Chem Inf
Model, 45, 1842 (2005) QSAR model for pK
constants of carboxylic acids and protonated
amines A. Cherkasov et al, J Phys Chem, 107, 9695
(2003) Descriptors-derived system for protein
charge calculation A. Cherkasov. J Chem Inf Comp
Sci, 43, 2039 (2003) QSAR model for dipole
moments A. Cherkasov et al, J. Mol. Struct.
Theochem, 497, 115 (2000) QSAR models for
oxidation energies of free radicals A Cherkasov
et al, J Chem Inf Comp Sci, 40, 1222 (2000), 39,
1057 (1999), 38, 1151 (1998) QSAR models for Gas
Basicity of Amines A. Cherkasov et al, J Mol
Graph Model, 17, 28 (1999) Predictive model for
inductive substituent constants. A. Cherkasov et
al, J Phys Org Chem 11, 437 (1998)
8
QSAR MODEL FOR ANTIBIOTICS
A mixture of known antibiotics and non-antibiotics
2/3 of all compounds for training
1/3 of all compounds for testing
Table 1Testing peptide classification
performance. QSAR - predictions based on QSAR
descriptors AA - predictions based on amino-acid
sequence only.
VALIDATION How the model performs on test
compounds
QSAR model for the training set
9
(No Transcript)
10
GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAA
TTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCT
GGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGG
GCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACAT
CTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGC
CCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAG
TGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTT
GCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTT
TGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGG
TTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGT
CTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCA
GGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTT
TATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAA
GCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTC
TGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATG
ATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGG
ATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGC
CCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGG
GAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACT
TTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCC
CATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGT
TTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTC
TGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAG
TAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAG
GGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTC
TCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGC
TGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCC
CAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAA
ACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG
GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGAT
CATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTT
CTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTG
ACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCA
GCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCC
AACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTA
GGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTG
CGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTT
CTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACC
CTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGG
AAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCC
TTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCA
CCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAG
TGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACAT
TTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACAT
ATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCA
GGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCA
CAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGC
CTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGA
GTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAA
GGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCC
AGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGA
GCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCA
TTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGG
GCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCC
TACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAG
TGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCT
GCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGG
CCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCAC
ATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACC
TGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCA
TTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTG
CCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGC
ACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGG
GTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATG
ACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACAC
AGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTA
AGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAG
GCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTT
CTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCT
GTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGT
CTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT
CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGC
TGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCA
AGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATG
TGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCT
CATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTT
GAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGC
AAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATG
GGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGA
GTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTC
TCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACC
TAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTT
GGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCC
CTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCA
GCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAG
GTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAG
GGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGA
TGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAA
CAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGT
CTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACA
GTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCC
AGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATT
TTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGG
CTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTC
GTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGG
AGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCG
CTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCG
TGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTG
GCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCG
AAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGG
AGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGAC
TCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGC
TCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCG
TGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGG
TGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCAC
TGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGC
TACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCA
TGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCA
CTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGA
AGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGG
CAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGT
CCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCC
CCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTG
TCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCT
GCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTT
CATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGA
CTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCA
CAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGC
TTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATT
CCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGG
GGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGT
CATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCC
AGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTT
GCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTC
TAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGG
AAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCA
GGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGC
TTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAA
GCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTT
CTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGA
GGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATT
CCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAA
ATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTG
ACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGN
GCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGG
GAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGAC
AGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGT
AGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTT
CCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGA
GGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCA
TGTTGAA
A number of QSAR models have been elaborated to
separate individual clusters within the dataset
of 958 human therapeutics, 519 antimicrobials,
1202 drug-like chemicals, as well as 1102
human-, 551 bacterial-, 2351 plant- and 825
fungal metabolites.
Antimicrobials from Drugs Antimicrobials from Drugs Antimicrobials from Drug-likes Antimicrobials from Drug-likes Distinguishing Antimicrobials from all others Distinguishing Antimicrobials from all others Distinguishing Antimicrobials versus Drugs versus Drug-likes Distinguishing Antimicrobials versus Drugs versus Drug-likes QSAR model for Bacterial Metabolites QSAR model for Bacterial Metabolites
Train Test Train Test Train Test Train Test Train Test
T_P 327 130 332 140 294 124 270 89 360 139
T_N 631 248 841 342 1490 621 1486 644 792 347
F_P 49 33 7 14 32 20 17 14 39 26
F_N 33 35 30 23 66 41 108 58 48 19
SPEC 0.93 0.88 0.99 0.96 0.98 0.97 0.99 0.98 0.95 0.93
SENS 0.91 0.79 0.92 0.86 0.82 0.75 0.71 0.61 0.88 0.88
ACCUR 0.92 0.85 0.97 0.93 0.95 0.92 0.93 0.91 0.93 0.92
PPV 0.87 0.80 0.98 0.91 0.90 0.86 0.94 0.86 0.90 0.84
NPV 0.95 0.88 0.97 0.94 0.96 0.94 0.93 0.92 0.94 0.95
THE UNIVERSITY OF BRITISH COLUMBIA MEDICINE
INFECTIOUS DISEASES
11
THE UNIVERSITY OF BRITISH COLUMBIA MEDICINE
INFECTIOUS DISEASES
12
Method Validation True Posit. TrueNegat FalsePosit. FalseNegat Spec. Sens. Accur PPV NPV
Antibacterials versus (Drugs Drug-likes Bacteria Metabolites Human Metabolites) Antibacterials versus (Drugs Drug-likes Bacteria Metabolites Human Metabolites) Antibacterials versus (Drugs Drug-likes Bacteria Metabolites Human Metabolites) Antibacterials versus (Drugs Drug-likes Bacteria Metabolites Human Metabolites) Antibacterials versus (Drugs Drug-likes Bacteria Metabolites Human Metabolites) Antibacterials versus (Drugs Drug-likes Bacteria Metabolites Human Metabolites) Antibacterials versus (Drugs Drug-likes Bacteria Metabolites Human Metabolites) Antibacterials versus (Drugs Drug-likes Bacteria Metabolites Human Metabolites) Antibacterials versus (Drugs Drug-likes Bacteria Metabolites Human Metabolites) Antibacterials versus (Drugs Drug-likes Bacteria Metabolites Human Metabolites) Antibacterials versus (Drugs Drug-likes Bacteria Metabolites Human Metabolites)
kNN Training 70 269 2610 9 95 0.97 0.74 0.95 0.80 0.96
kNN Testing 30 117 1119 8 39 0.98 0.75 0.95 0.81 0.97
kNN LOO 400 3727 9 120 0.97 0.77 0.95 0.80 0.97
LDA Training 70 364 0 2679 0 0.00 1.00 0.12 0.12 0.00
LDA Testing 30 156 0 1147 0 0.00 1.00 0.12 0.12 0.00
LDA LOO 261 3751 75 259 0.98 0.50 0.92 0.78 0.94
MLR Training 70 194 564 2115 170 0.21 0.53 0.25 0.08 0.77
MLR Testing 30 61 1129 18 95 0.98 0.39 0.91 0.77 0.92
MLR LOO 279 3726 100 241 0.97 0.54 0.92 0.74 0.94
ANN Training 70 294 2651 27 70 0.99 0.81 0.97 0.92 0.97
ANN Testing 30 129 1132 16 27 0.99 0.83 0.97 0.89 0.98
ANN LOO 449 3821 5 71 0.99 0.86 0.98 0.99 0.98
Bacteria Metabolites versus (Drugs Drug-likes Antibacterials Human Metabolites) Bacteria Metabolites versus (Drugs Drug-likes Antibacterials Human Metabolites) Bacteria Metabolites versus (Drugs Drug-likes Antibacterials Human Metabolites) Bacteria Metabolites versus (Drugs Drug-likes Antibacterials Human Metabolites) Bacteria Metabolites versus (Drugs Drug-likes Antibacterials Human Metabolites) Bacteria Metabolites versus (Drugs Drug-likes Antibacterials Human Metabolites) Bacteria Metabolites versus (Drugs Drug-likes Antibacterials Human Metabolites) Bacteria Metabolites versus (Drugs Drug-likes Antibacterials Human Metabolites) Bacteria Metabolites versus (Drugs Drug-likes Antibacterials Human Metabolites) Bacteria Metabolites versus (Drugs Drug-likes Antibacterials Human Metabolites) Bacteria Metabolites versus (Drugs Drug-likes Antibacterials Human Metabolites)
kNN Training 70 311 2537 112 83 0.96 0.79 0.94 074 0.97
kNN Testing 30 135 1091 44 33 0.96 0.80 0.94 0.75 0.97
kNN LOO 455 3637 147 107 0.96 0.81 0.94 0.76 0.97
LDA Training 70 240 2587 62 154 0.98 0.61 0.93 0.79 0.94
LDA Testing 30 90 1088 47 78 0.96 0.54 0.90 0.66 0.93
LDA LOO 336 3665 119 226 0.97 0.60 0.92 0.74 0.94
MLR Training 70 301 2525 124 93 0.95 0.76 0.93 0.71 0.96
MLR Testing 30 119 1073 62 49 0.95 0.71 0.91 0.66 0.96
MLR LOO 406 3603 181 156 0.95 0.72 0.92 0.69 0.96
ANN Training 70 338 2597 52 55 0.98 0.86 0.96 0.87 0.98
ANN Testing 30 159 1076 59 10 0.95 0.94 0.95 0.73 0.99
ANN LOO 534 3780 4 28 0.99 0.95 0.99 0.99 0.99
THE UNIVERSITY OF BRITISH COLUMBIA MEDICINE
INFECTIOUS DISEASES
13
GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAA
TTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCT
GGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGG
GCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACAT
CTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGC
CCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAG
TGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTT
GCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTT
TGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGG
TTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGT
CTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCA
GGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTT
TATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAA
GCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTC
TGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATG
ATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGG
ATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGC
CCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGG
GAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACT
TTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCC
CATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGT
TTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTC
TGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAG
TAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAG
GGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTC
TCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGC
TGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCC
CAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAA
ACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG
GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGAT
CATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTT
CTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTG
ACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCA
GCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCC
AACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTA
GGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTG
CGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTT
CTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACC
CTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGG
AAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCC
TTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCA
CCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAG
TGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACAT
TTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACAT
ATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCA
GGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCA
CAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGC
CTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGA
GTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAA
GGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCC
AGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGA
GCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCA
TTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGG
GCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCC
TACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAG
TGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCT
GCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGG
CCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCAC
ATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACC
TGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCA
TTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTG
CCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGC
ACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGG
GTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATG
ACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACAC
AGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTA
AGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAG
GCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTT
CTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCT
GTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGT
CTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT
CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGC
TGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCA
AGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATG
TGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCT
CATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTT
GAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGC
AAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATG
GGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGA
GTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTC
TCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACC
TAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTT
GGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCC
CTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCA
GCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAG
GTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAG
GGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGA
TGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAA
CAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGT
CTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACA
GTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCC
AGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATT
TTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGG
CTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTC
GTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGG
AGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCG
CTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCG
TGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTG
GCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCG
AAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGG
AGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGAC
TCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGC
TCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCG
TGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGG
TGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCAC
TGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGC
TACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCA
TGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCA
CTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGA
AGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGG
CAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGT
CCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCC
CCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTG
TCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCT
GCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTT
CATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGA
CTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCA
CAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGC
TTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATT
CCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGG
GGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGT
CATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCC
AGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTT
GCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTC
TAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGG
AAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCA
GGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGC
TTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAA
GCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTT
CTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGA
GGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATT
CCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAA
ATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTG
ACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGN
GCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGG
GAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGAC
AGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGT
AGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTT
CCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGA
GGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCA
TGTTGAA
THE UNIVERSITY OF BRITISH COLUMBIA MEDICINE
INFECTIOUS DISEASES
14
Separation of various classes of substances in
the chemical space
General drugs
Bacterial metabolites
Inactive Chemicals
Antibacterials
15
2. Finding potential antibiotics among common
drugs, substances
16
Bad Bugs Need Drugs IDSA, March 2006
Antimicrobial Availability Task Force
Widespread prevalence of MDR bacteria in
hospitals Few drugs in a pipeline, Urgent need
for RD
Experts Fear Increase in Drug-resistant
Infectious Here Globe and Mail, March 2006
MRSA, a treatment-resistant form of bacteria that
spreads through direct contact, is called a
greater threat to public health than SARS or bird
flu. The Boston Globe, August 21, 2006
17
Resistance mechanisms are very effective
(specific toward the existing antibiotics)
18
Resistance mechanisms are very effective
(specific toward the existing antibiotics)
Lateral gene transfer
19
Resistance mechanisms are very effective
(specific toward the existing antibiotics)
Lateral gene transfer
Active transport
20
Resistance mechanisms are very effective
(specific toward the existing antibiotics)
Lateral gene transfer
Active transport
Resistant mutations
21
Resistance mechanisms are very effective
(specific toward the existing antibiotics)
Lateral gene transfer
Active transport
Resistant mutations
BUT off-target bacterial inhibition by
non-antibiotics might still work
22
Resistance mechanisms are very effective
(specific toward the existing antibiotics)
Lateral gene transfer
Active transport
Resistant mutations
BUT off-target bacterial inhibition by
non-antibiotics might still work NEED TO FIND
SUCH AB-LIKE DRUGS
23
GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAA
TTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCT
GGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGG
GCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACAT
CTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGC
CCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAG
TGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTT
GCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTT
TGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGG
TTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGT
CTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCA
GGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTT
TATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAA
GCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTC
TGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATG
ATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGG
ATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGC
CCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGG
GAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACT
TTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCC
CATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGT
TTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTC
TGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAG
TAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAG
GGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTC
TCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGC
TGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCC
CAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAA
ACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG
GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGAT
CATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTT
CTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTG
ACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCA
GCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCC
AACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTA
GGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTG
CGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTT
CTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACC
CTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGG
AAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCC
TTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCA
CCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAG
TGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACAT
TTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACAT
ATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCA
GGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCA
CAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGC
CTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGA
GTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAA
GGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCC
AGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGA
GCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCA
TTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGG
GCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCC
TACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAG
TGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCT
GCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGG
CCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCAC
ATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACC
TGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCA
TTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTG
CCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGC
ACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGG
GTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATG
ACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACAC
AGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTA
AGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAG
GCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTT
CTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCT
GTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGT
CTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT
CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGC
TGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCA
AGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATG
TGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCT
CATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTT
GAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGC
AAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATG
GGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGA
GTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTC
TCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACC
TAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTT
GGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCC
CTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCA
GCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAG
GTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAG
GGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGA
TGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAA
CAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGT
CTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACA
GTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCC
AGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATT
TTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGG
CTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTC
GTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGG
AGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCG
CTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCG
TGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTG
GCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCG
AAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGG
AGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGAC
TCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGC
TCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCG
TGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGG
TGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCAC
TGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGC
TACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCA
TGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCA
CTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGA
AGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGG
CAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGT
CCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCC
CCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTG
TCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCT
GCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTT
CATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGA
CTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCA
CAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGC
TTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATT
CCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGG
GGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGT
CATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCC
AGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTT
GCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTC
TAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGG
AAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCA
GGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGC
TTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAA
GCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTT
CTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGA
GGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATT
CCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAA
ATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTG
ACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGN
GCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGG
GAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGAC
AGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGT
AGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTT
CCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGA
GGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCA
TGTTGAA
THE UNIVERSITY OF BRITISH COLUMBIA MEDICINE
INFECTIOUS DISEASES
24
MERCK Database scaning
GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAA
TTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCT
GGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGG
GCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACAT
CTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGC
CCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAG
TGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTT
GCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTT
TGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGG
TTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGT
CTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCA
GGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTT
TATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAA
GCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTC
TGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATG
ATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGG
ATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGC
CCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGG
GAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACT
TTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCC
CATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGT
TTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTC
TGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAG
TAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAG
GGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTC
TCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGC
TGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCC
CAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAA
ACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG
GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGAT
CATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTT
CTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTG
ACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCA
GCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCC
AACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTA
GGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTG
CGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTT
CTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACC
CTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGG
AAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCC
TTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCA
CCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAG
TGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACAT
TTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACAT
ATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCA
GGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCA
CAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGC
CTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGA
GTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAA
GGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCC
AGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGA
GCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCA
TTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGG
GCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCC
TACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAG
TGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCT
GCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGG
CCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCAC
ATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACC
TGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCA
TTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTG
CCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGC
ACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGG
GTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATG
ACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACAC
AGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTA
AGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAG
GCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTT
CTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCT
GTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGT
CTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT
CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGC
TGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCA
AGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATG
TGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCT
CATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTT
GAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGC
AAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATG
GGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGA
GTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTC
TCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACC
TAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTT
GGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCC
CTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCA
GCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAG
GTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAG
GGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGA
TGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAA
CAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGT
CTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACA
GTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCC
AGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATT
TTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGG
CTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTC
GTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGG
AGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCG
CTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCG
TGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTG
GCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCG
AAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGG
AGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGAC
TCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGC
TCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCG
TGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGG
TGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCAC
TGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGC
TACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCA
TGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCA
CTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGA
AGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGG
CAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGT
CCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCC
CCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTG
TCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCT
GCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTT
CATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGA
CTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCA
CAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGC
TTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATT
CCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGG
GGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGT
CATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCC
AGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTT
GCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTC
TAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGG
AAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCA
GGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGC
TTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAA
GCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTT
CTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGA
GGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATT
CCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAA
ATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTG
ACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGN
GCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGG
GAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGAC
AGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGT
AGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTT
CCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGA
GGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCA
TGTTGAA
THE UNIVERSITY OF BRITISH COLUMBIA MEDICINE
INFECTIOUS DISEASES
25
MERCK Database scaning
GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAA
TTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCT
GGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGG
GCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACAT
CTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGC
CCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAG
TGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTT
GCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTT
TGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGG
TTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGT
CTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCA
GGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTT
TATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAA
GCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTC
TGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATG
ATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGG
ATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGC
CCTGGCTCTGTCTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGG
GAGCTGGGTGTCAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACT
TTCCAGTTTGCTGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCC
CATCCACCCCAAGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGT
TTTCCTGCATGTGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTC
TGCTGTGCCCTCATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAG
TAGGTGCCCTTGAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAG
GGATCCAGGGCAAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTC
TCAGGGGAATGGGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGC
TGGCTGGACGAGTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCC
CAGTCTTGGTCTCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAA
ACTTGATGACCTAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTG
GCGCTGGACTTGGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGAT
CATCCCTATCCCTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTT
CTGTAGCCCCAGCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTG
ACCCCCTCCAGGTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCA
GCTGGGCCCAGGGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCC
AACCAGGGAGATGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTA
GGGGATGGAAACAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTG
CGAGAAAATGTCTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTT
CTGAGCCCACAGTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACC
CTCCCCTTGCCAGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGG
AAGACTTGATTTTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCC
TTCAAGTTGGGCTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCA
CCTTGGCCCTCGTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAG
TGGGCGGAGGGAGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACAT
TTCACAAGCCGCTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACAT
ATTTCGGAGCGTGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCA
GGACCTCCCTGGCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCA
CAGGCCTGGCGAAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGC
CTTACCCGAGGAGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGA
GTCAGGGAGACTCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAA
GGAGCCATGGCTCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCC
AGGCTCCTGCGTGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGA
GCTCCCATTGGTGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCA
TTCCCTCTCACTGTCCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGG
GCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAATTTGCATTCCC
TACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAG
TGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCT
GCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGG
CCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCAC
ATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAGTGGAAGTGACC
TGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCA
TTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTG
CCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGC
ACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGG
GTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATG
ACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACAC
AGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTA
AGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTCTGGAAGATGAG
GCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATGATCCACATTTT
CTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCT
GTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGT
CTCCAGGACCTCTTCTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGT
CAACCTGTGCCCGAGGAAATCATACAGTTACTGTGGACTTTCCAGTTTGC
TGTCTTCTAGTATTCCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCA
AGATCCAGCTGGAAATCAGTGAACACACTTGATGGGAGTTTTCCTGCATG
TGCTCTGGGCATTGACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCT
CATGGAGGAAGAGNGCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTT
GAGCCCAGCTTTGGGAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGC
AAAGCAGGCACGACAGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATG
GGCATGGAGTGGGTAGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGA
GTCAGGAGCCCCTTCCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTC
TCCTGCATGCCAGAGGTACCAGCCCATCTTTTTTCCTAAACTTGATGACC
TAGGGCTAGGGGCATGTTGAATCTCAGCCTCGCCCACTGGCGCTGGACTT
GGTACACAGGGTGGGGCAAAGTGGGTACTGGATCCTGATCATCCCTATCC
CTGGGGTGTGGCTTCTTGCTGCACAGTCAGCTTCTAGTTCTGTAGCCCCA
GCTGCTCCTGCGGTGGAGGGAGCTACACATCAGGCTCTGACCCCCTCCAG
GTGGGGCCTTCGCGTGAGGGGAGTCAGCACGCATCAGCAGCTGGGCCCAG
GGAGTTGCCCCACTGAGCACTGCGGGCTGACCTGCTCCCAACCAGGGAGA
TGGAGCTTCCCCCTTGAGTCGGGCTGCTGAAGGGGGGTAGGGGATGGAAA
CAGTGCGTTTGCAGGAGTAAGGGTGCAGTTGGGTCCCTGCGAGAAAATGT
CTCAGTTGTGGCAACTGATTGGTGACCTGGGGGGCGTTTCTGAGCCCACA
GTGCTGGCATCAGGACTCAGGTGTGAGGTGCCCCAGACCCTCCCCTTGCC
AGTAATTAGCTGATGGCTCGGTGATGCCCAGGGTGAAGGAAGACTTGATT
TTGGGAGGGGAGTTCTCTCGTAATGACACTGAGGATGCCTTCAAGTTGGG
CTTCTGGCATGTTCTGCCCTCGCTCCCCTTCTGTAGTCACCTTGGCCCTC
GTGTTGCTGAGCTGTGTGTGGGAGCGGGAAGCGCGTCAGTGGGCGGAGGG
AGCGGGAAGCGCGTCAGTGGGCGGAGTATTTGAGAACATTTCACAAGCCG
CTGTTGAGGTTCAGAATCAACCAGCAGATACAGAAACATATTTCGGAGCG
TGGGGACCCTTGGGTGAGCTGCCACATGAAGCAGCCCCAGGACCTCCCTG
GCTCAAGGAGTGACAGCGAGTTTGTCTGAGGTGAGGGCACAGGCCTGGCG
AAGCCTCGTGTGTGGGTGAGACCTGCCCGACCCCAGTGCCTTACCCGAGG
AGCTACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGAC
TCATGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGC
TCACTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCG
TGAAGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGG
TGGCAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCAC
TGTCCTGGAGAGGACGAGAATTCCACCTGCCAGTGCCTTACCCGAGGAGC
TACTGGCCCAGTGGGGGAGGCATTCAGGTGGGCAGAGTCAGGGAGACTCA
TGAGGCCGTTGAGGCCAGGGGCATAGAGCTGGCCAAGGAGCCATGGCTCA
CTAACGTGTTGTATGGGGCTCCTTCCCTTCAGGTCCAGGCTCCTGCGTGA
AGTGATGCTCCTCTTTGCCTTACTCCTAGCCATGGAGCTCCCATTGGTGG
CAGCCAGTGCCACCATCGCGCTCAGTGTAAGTATCATTCCCTCTCACTGT
CCTGGAGAGGACGAGAATTCCACCTGGAGATTCTGGGCCACTTTGGTTCC
CCATGAGCCAAGACGGCACTTCTAATTTGCATTCCCTACCGGAGTCCCTG
TCTGTAGCCAGCCTGGCTTTCAGCTGGTGCCCAAAGTGACAAATGTATCT
GCAATGACAAAGGTACCCTGGAAGGGCTCGCCCTCTGCGGAATTTCAGTT
CATGCAGGCCTTGGTGCTTCCACATCTGTCCAAGGGCCTTTCAAATGTGA
CTTTTAACTCTGTGGATTGATTTGCCCGGTTGTCACATTCTGAGCAGCCA
CAACCTACTGCATCCCATGTAGAAGTGGAAGTGACCTGATTTTTTCCTGC
TTTTCAAGGCTGTATGTTTACATTTGCCTCCAATCATTCCTATGGGAATT
CCTTGGGAGTCTAACTTGGAGATTTTGTTTCTTCTGCCTTTGCTCCTGGG
GGCTTAATCACTTCTGTGCCTCTGGTTATCTGTGGCACATTTGTATTTGT
CATTAGTCAACCGGAGACTCGGGGTCTGAGTGGAGGGTATGTCCCCCTCC
AGTGATGGTTTCTGTTGGCTTCCCAGGGTGAGGATGACTCATGACCACTT
GCAAGTGGTTTTTGTGTCTGGGGTTTATGATCACACAGTCATACACGTTC
TAACTCCAGACTGACTGTTGAGAAAGCCTCTGGGTAAGGGAATTCCTGGG
AAACACACTGTTTTCATGCATCCTCTGGAAGATGAGGCCTGAAGTTACCA
GGGTCTCTGTTTGCTGATGCTGATGATCCACATTTTCTAGCCCACTCTGC
TTCTCTGACACCTTTAGTCTTGAGGATCCATGNTCTGTGAAGGAATCCAA
GCTCTCATTTCGCACTCACCTTGGCCCTGGCTCTGTCTCCAGGACCTCTT
CTACTACAAAATCCTAAAGCTCTGGGAGCTGGGTGTCAACCTGTGCCCGA
GGAAATCATACAGTTACTGTGGACTTTCCAGTTTGCTGTCTTCTAGTATT
CCATTGTAGCTCTTGGGTATTTTCCCATCCACCCCAAGATCCAGCTGGAA
ATCAGTGAACACACTTGATGGGAGTTTTCCTGCATGTGCTCTGGGCATTG
ACAGTAGAAGGGTGTTCAGAATGTCTGCTGTGCCCTCATGGAGGAAGAGN
GCTCAGTGTACATGCTCTGGGTCAGTAGGTGCCCTTGAGCCCAGCTTTGG
GAGCAATGTTGGATGAGTGAAGGAGGGATCCAGGGCAAAGCAGGCACGAC
AGAGTGGAGACGGCGCTGCTGGCTCTCAGGGGAATGGGCATGGAGTGGGT
AGGAGATCCACCTAAGGAGGCTGGCTGGCTGGACGAGTCAGGAGCCCCTT
CCAAGGGTGGACACTGACAGGCCCCCAGTCTTGGTCTCCTGCATGCCAGA
GGTACCAGCCCATCTTTTTTCCTAAACTTGATGACCTAGGGCTAGGGGCA
TGTTGAA
CONFIRMED
CONFIRMED
CONFIRMED
THE UNIVERSITY OF BRITISH COLUMBIA MEDICINE
INFECTIOUS DISEASES
26
3. Attacking essential proteins in emerging
and re-emerging pathogens Prospectives,
Protocols
27
(No Transcript)
28
PINs
GGAGATTCTGGGCCACTTTGGTTCCCCATGAGCCAAGACGGCACTTCTAA
TTTGCATTCCCTACCGGAGTCCCTGTCTGTAGCCAGCCTGGCTTTCAGCT
GGTGCCCAAAGTGACAAATGTATCTGCAATGACAAAGGTACCCTGGAAGG
GCTCGCCCTCTGCGGAATTTCAGTTCATGCAGGCCTTGGTGCTTCCACAT
CTGTCCAAGGGCCTTTCAAATGTGACTTTTAACTCTGTGGATTGATTTGC
CCGGTTGTCACATTCTGAGCAGCCACAACCTACTGCATCCCATGTAGAAG
TGGAAGTGACCTGATTTTTTCCTGCTTTTCAAGGCTGTATGTTTACATTT
GCCTCCAATCATTCCTATGGGAATTCCTTGGGAGTCTAACTTGGAGATTT
TGTTTCTTCTGCCTTTGCTCCTGGGGGCTTAATCACTTCTGTGCCTCTGG
TTATCTGTGGCACATTTGTATTTGTCATTAGTCAACCGGAGACTCGGGGT
CTGAGTGGAGGGTATGTCCCCCTCCAGTGATGGTTTCTGTTGGCTTCCCA
GGGTGAGGATGACTCATGACCACTTGCAAGTGGTTTTTGTGTCTGGGGTT
TATGATCACACAGTCATACACGTTCTAACTCCAGACTGACTGTTGAGAAA
GCCTCTGGGTAAGGGAATTCCTGGGAAACACACTGTTTTCATGCATCCTC
TGGAAGATGAGGCCTGAAGTTACCAGGGTCTCTGTTTGCTGATGCTGATG
ATCCACATTTTCTAGCCCACTCTGCTTCTCTGACACCTTTAGTCTTGAGG
ATCCATGNTCTGTGAAGGAATCCAAGCTCTCATTTCGCACTCACCTTGGC
CCTGGCTCTGTCTCCAGGA