Toward Improved Force-Field Accuracy through Sensitivity Analysis of Host-Guest Binding Thermodynamics.

ABSTRACT: Improving the capability of atomistic computer models to predict the thermodynamics of noncovalent binding is critical for successful structure-based drug design, and the accuracy of such calculations remains limited by nonoptimal force field parameters. Ideally, one would incorporate protein-ligand affinity data into force field parametrization, but this would be inefficient and costly. We now demonstrate that sensitivity analysis can be used to efficiently tune Lennard-Jones parameters of aqueous host-guest systems for increasingly accurate calculations of binding enthalpy. These results highlight the promise of a comprehensive use of calorimetric host-guest binding data, along with existing validation data sets, to improve force field parameters for the simulation of noncovalent binding

SUBMITTER: Yin J 

PROVIDER: S-EPMC4664157 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature