Insights into the phosphoryl-transfer mechanism of cAMP-dependent protein kinase from quantum chemical calculations and molecular dynamics simulations.

摘要: To investigate the molecular details of phosphoryl-transfer mechanism catalyzed by cAMP-dependent protein kinase, we performed quantum mechanical (QM) calculations on a cluster model active site and dynamics (MD) simulations ternary complex with Mg 2 ATP 20-residue peptide substrate. Overall, our theoretical results confirm participation conserved aspartic acid, Asp 166 , as an acid/base catalyst in reaction kinases. The MD simulation shows that contact between nucleophilic serine side chain carboxylate group is short dynamically stable, whereas OM study indicates -assisted pathway structurally energetically feasible agreement previous experimental results.