How inaccuracies in protein structure models affect estimates of protein-ligand interactions: computational analysis of HIV-I protease inhibitor binding.

摘要: The influence of possible inaccuracies that can arise during homology modeling protein structures used for ligand binding studies were investigated with the molecular mechanics generalized Born surface area (MM-GBSA) method. For this, a family well-characterized HIV-I protease-inhibitor complexes was used. Validation MM-GBSA led to correlation coefficient ranging from 0.72 0.93 between calculated and experimental free energies DeltaG. All DeltaG values based on dynamics simulations explicit solvent. Errors introduced into structure through misplacement side-chains rotamer DeltaG(calc) DeltaG(exp) 0.75 compared 0.90 correctly placed side chains. This is in contrast models members retroviral protease template sequence identity 32% 51%. these models, coefficients vary 0.84 0.87, which considerably closer original (0.90). It concluded low still allows creating sufficiently reliable be ligand-binding studies, although placement rotamers critical step modeling.