Four-body atomic potential for modeling protein-ligand binding affinity: application to enzyme-inhibitor binding energy prediction.

ABSTRACT:

Background

Models that are capable of reliably predicting binding affinities for protein-ligand complexes play an important role the field of structure-guided drug design.

Methods

Here, we begin by applying the computational geometry technique of Delaunay tessellation to each set of atomic coordinates for over 1400 diverse macromolecular structures, for the purpose of deriving a four-body statistical potential that serves as a topological scoring function. Next, we identify a second, independent set of three hundred protein-ligand complexes, having both high-resolution structures and known dissociation constants. Two-thirds of these complexes are randomly selected to train a predictive model of binding affinity as follows: two tessellations are generated in each case, one fo

SUBMITTER: Masso M 

PROVIDER: S-EPMC3952120 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature