Ensemble Results of PIM1

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Ensemble Results of PIM1
PIM1-77-5
PIM1-15-6
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Ensemble Results of GSK3
GSK3-79-2
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Ensemble Results of EGFR
EGFR-0-5
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GSK3
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EGFR
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-2.74
-0.54
-2.91
0.27
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Conformations Predicted Using Single Conformation
Docking
GSK3-rank-1
GSK3-rank-2
GLU97
ARG133
ARG133
Binding mode of kinases complexed with
Ru-inhibitor, HB12. BLUE is the crystal
conformation and Purple is obtained using single
conformation molecular docking. Predictions of
the location and conformation of the bound ligand
in PIM1 matched the crystallographic data very
closely as shown in Figure. With GSK3ß, HB12
shows multiple binding conformations, see Figure.
In the lowest binding energy conformation
(rank1), the compound forms a hydrogen bond with
residue GLU97. Another conformation is also
predicted characterized by a hydrogen bond with
residue ASP133 (corresponding residue in PIM1 is
GLU121), however, the inhibitor itself is rotated
180 in comparison with the bound conformations.
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The Most Productive Conformations from Ensemble
Docking
PIM1
GSK3
ARG133
GLU121
Blue Crystal Structures (PIM1 2BZH.pdb, GSK3,
Unpublished) Purple Predicted Structures The two
predicted conformations are within 2.0 angstroms
compared with the Crystal structure.
Conformations showed here are the most productive
(lowest energy with entropy correction for PIM1
and GSK3)
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Conformation Fluctuation in Cluster
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• Slices after this are backup slices which show
  the conformations in detail.

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GSK3-63-18
ASN64
LEU132
LYS85
TYR134
ASP133
ASP200
LEU188
ASN186
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GSK3-59-2
ASN64
LYS85
LEU132
ASP133
ASP200
TYR134
GLN185
LEU188
ASN186
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EGFR-0-5
SER696
LEU768
THR766
GLN767
ASP831
MET769
ASN818
ARG817
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EGFR-70-25
SER696
THR766
GLN767
LEU768
ASP831
MET769
ASN818
ARG817
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EGFR-89-6
THR766
GLN767
LEU768
MET769
ASP831
ASN818
LEU820
ARG817
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EGFR-0-19
THR766
GLN767
LEU768
ASP831
MET769
ASN818
LEU820
ARG817
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PIM1-77-5
LYS67
GLY45
LEU120
GLU121
ASP186
LEU174
ASN172
GLU171