Alignment of Targetable Molecular Features Across the Human Kinome

2 Alignment of Targetable Molecular Features Across the Human Kinome 

Consequently, a reliable sequence-based predictor of the relevant molecular attributes of kinases had to be implemented as shown in the previous sections. 

64 PRKAAl 04 PEMACA 09 PT 3 07 PTW 66 RlOk3 66 RPS6MC 100 RP96RM 1D1 RPSOMW 

To determine whether pharmacological differences are dictated by differences in nonpolar accessible surfaces of the targets within ligand-binding sites, a nonpolar distance, dnp (i,j), between the affinity-assayed kinases i, j is introduced. The dnp (i,j) is determined by differences in accessible nonpolar surface areas of the respective nonpolar hulls, Hnp ( ), Hnp (j). As rigorously defined in the previous 

Only 32 of the 119 assayed kinases are reported in PDB complexes, yet, structural inferences can be made with confidence given the significant extent of structural alignment (RMSD 1 A) across reported structures [10]. The prediction accuracy decreases somewhat but in a quantifiable manner (—12%) on loopy regions [10]. The matrix Dnp = dap (/,/)] (Fig. 9.1c) reveals remarkable nonpolar similarity across kinases dap /(maximum (dnp) — 11%( = average over 

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