Computer-aided Drug Discovery G.P.S. Raghava

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Computer-aided Drug Discovery G.P.S. Raghava

• Annotation of genomes
• Searching drug targets
• Properties of drug molecules
• Protein-chemical interaction
• Prediction of drug-like molecules

Drug Informatics
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• Comparative genomics
• GWFASTA Genome Wide FASTA Search
• Analysis of FASTA search for comparative genomics
• Biotechniques 2002, 33548
• GWBLAST Genome wide BLAST search
• COPID Composition based similarity search
• LGEpred Expression of a gene from its Amino acid
  sequence
• BMC Bioinformatics 2005, 659
• ECGpred Expression from its nucleotide sequence

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• Subcellular localization Methods
• PSLpred Subcellular localization of prokaryotic
  proteins
• 5 major sub cellular localization
• Bioinformatics 2005, 21 2522
• ESLpred Subcellular localization of Eukaryotic
  proteins
• SVM based method
• Amino acid, Dipetide and properties composition
• Sequence profile (PSIBLAST)
• Nucleic Acids Research 2004, 32W414-9
• HSLpred Sub cellular localization of Human
  proteins
• Need to develop organism specific methods
• 84 accuracy for human proteins
• Journal of Biological Chemistry 2005,
  28014427-32
• MITpred Prediction of Mitochndrial proteins
• Exclusive mitochndrial domain and SVM
• J Biol Chem. 2005, 2815357-63.
• Tbpred Subcellular Localization of Mycobaterial
  Proteins (M.Tb)
• BMC Bioinformatics 2007,
• Work in Progress Subcellular localization of
  malaria

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• Regular Secondary Structure Prediction (?-helix
  ?-sheet)
• APSSP2 Highly accurate method for secondary
  structure prediction
• Competete in EVA, CAFASP and CASP (In top 5
  methods)
• Irregular secondary structure prediction methods
  (Tight turns)
• Betatpred Consensus method for ?-turns
  prediction
• Statistical methods combined
• Kaur and Raghava (2001) Bioinformatics
• Bteval Benchmarking of ?-turns prediction
• Kaur and Raghava (2002) J. Bioinformatics and
  Computational Biology, 1495504
• BetaTpred2 Highly accurate method for predicting
  ?-turns (ANN, SS, MA)
• Multiple alignment and secondary structure
  information
• Kaur and Raghava (2003) Protein Sci 12627-34
• BetaTurns Prediction of ?-turn types in proteins
  
• Kaur and Raghava (2004) Bioinformatics 202751-8.
  
• AlphaPred Prediction of ?-turns in proteins
• Kaur and Raghava (2004) Proteins Structure,
  Function, and Genetics 5583-90
• GammaPred Prediction of ?-turns in proteins
• Kaur and Raghava (2004) Protein Science
  12923-929.

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• Supersecondary Structure
• BhairPred Prediction of Beta Hairpins
• Secondary structure and surface accessibility
  used as input
• Manish et al. (2005) Nucleic Acids Research
  33W154-9
• TBBpred Prediction of outer membrane proteins
• Prediction of trans membrane beta barrel proteins
• Application of ANN and SVM Evolutionary
  information
• Natt et al. (2004) Proteins 5611-8
• ARNHpred Analysis and prediction side chain,
  backbone interactions
• Prediction of aromatic NH interactions
• Kaur and Raghava (2004) FEBS Letters 56447-57 .
• Chpredict Prediction of C-H .. O and PI
  interaction
• Kaur and Raghava (2006) In-Silico Biology 60011
• SARpred Prediction of surface accessibility
  (real accessibility)
• Multiple alignment (PSIBLAST) and Secondary
  structure information
• Garg et al., (2005) Proteins 61318-24
• Secondary to Tertiary Structure
• PepStr Prediction of tertiary structure of
  Bioactive peptides
• Kaur et al. (2007) Protein Pept Lett. (In Press)

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• Nrpred Classification of nuclear receptors
• BLAST fails in classification of NR proteins
• Uses composition of amino acids
• Journal of Biological Chemistry 2004, 279 23262
• GPCRpred Prediction of G-protein-coupled
  receptors
• Predict GPCR proteins class
• gt 80 in Class A, further classify
• Nucleic Acids Research 2004, 32W383
• GPCRsclass Amine type of GPCR
• Major drug targets, 4 classes,
• Accuracy 96.4
• Nucleic Acids Research 2005, 33W172
• VGIchanVoltage gated ion channel
• Genomics Proteomics Bioinformatics 2007,
  4253-8
• Pprint RNA interacting residues in proteins
• Proteins Structure, Function and Bioinformatics
  (In Press)
• GSTpred Glutathione S-transferases proteins
• Protein Pept Lett. 2007, 6575-80

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• Antibp Analysis and prediction of antibacterial
  peptides
• Searching and mapping of antibacterial peptide
• BMC Bioinformatics 2007, 8263
• ALGpred Prediction of allergens
• Using allergen representative peptides
• Nucleic Acids Research 2006, 34W202-9.
• BTXpred Prediction of bacterial toxins
• Classifcation of toxins into exotoxins and
  endotoxins
• Classification of exotoxins in seven classes
• In Silico Biology 2007, 7 0028
• NTXpred Prediction of neurotoxins
• Classification based on source
• Classification based on function (ion channel
  blockers, blocks Acetylcholine receptors etc.)
• In Silico Biology 2007, 7, 0025

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• Work in Progress (Future Plan)
• Prediction of solubility of proteins and peptides
• Understand drug delivery system for protein
• Degradation of proteins
• Improving thermal stability of a protein (Protein
  Science 122118-2120)
• Analysis and prediction of druggable
  proteins/peptide

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• MELTpred Prediction of melting point of chemical
  compunds
• Around 4300 compounds were analzed to derive
  rules
• Successful predicted melting point of 277
  drug-like molecules
• Future Plan
• QSAR models for ADMET
• QSAR docking for ADMET
• Prediction of drug like molecules
• Open access in Chemoinformatics

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• Understanding Protein-Chemical Interaction
• Prediction of Kinases Targets and Off Targets
• Kinases inhibitors were analyzed
• Model build to predict inhbitor against kinases
• Cross-Specificity were checked
• Useful for predicting targets and off targets
• DMKpred Prediction of binding affinity of drug
  molecules with kinase
• Future Plan
• Classification of proteins based on chemical
  interaction
• Clustering drug molecules based on interaction
  with proteins

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Thankyou