Profile Analysis of ATP, p38 and CDK2 Complexes

A convenient way to compare directly the p-SIFts is to define a difference profile computed by the direct subtraction of one p-SIFt from another. The differ- 

Three major clusters (1-3) are labeled on the left side of the heat map and also a cluster corresponding to the DFG-out conformation of the kinases, (b) Comparison of the binding modes of the three different kinase clusters. 

216 I 70 SIFt Analysis, Organization and Database Mining for Protein-Inhibitor Complexes 

Unlike contacts with the hydrophobic pocket, several interactions conserved in the p38 cluster are common to CDK2, and also other non-ATP inhibitors. Finally, several interactions are conserved for ATPg and are observed with relatively low frequency for CDK2 and p38. These ATPg-specific contacts involve residues at positions 50-55, which interact with the ribose and phosphate moieties of ATP and with residues at positions 168, 170 and 171, in the vicinity of the catalytic loop. 

SIFt scoring approach. For p38, the 11ybrid Scoring scheme (p-SIFT to rule out undesirable poses followed by energy scoring function identify and rank the best pose) was found to offer no improvement in enrichment over that obtained from using p-SIFt scoring. 

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