A combination of docking, QM/MM methods, and MD simulation for binding affinity estimation of metalloprotein ligands.

ABSTRACT: To alleviate the problems in the receptor-based design of metalloprotein ligands due to inadequacies in the force-field description of coordination bonds, a four-tier approach was devised. Representative ligand-metalloprotein interaction energies are obtained by subsequent application of (1) docking with metal-binding-guided selection of modes, (2) optimization of the ligand-metalloprotein complex geometry by combined quantum mechanics and molecular mechanics (QM/MM) methods, (3) conformational sampling of the complex with constrained metal bonds by force-field-based molecular dynamics (MD), and (4) a single point QM/MM energy calculation for the time-averaged structures. The QM/MM interaction energies are, in a linear combination with the desolvation-characterizing changes in the solvent-

SUBMITTER: Khandelwal A 

PROVIDER: S-EPMC2896055 | biostudies-literature | 2005 Aug

REPOSITORIES: biostudies-literature