Ligand-Binding-Site Refinement to Generate Reliable Holo Protein Structure Conformations from Apo Structures.

ABSTRACT: The first important step in a structure-based virtual screening is the judicious selection of a receptor protein. In cases where the holo protein receptor structure is unavailable, significant reduction in virtual screening performance has been reported. In this work, we present a robust method to generate reliable holo protein structure conformations from apo structures using molecular dynamics (MD) simulation with restraints derived from holo structure binding-site templates. We perform benchmark tests on two different datasets: 40 structures from a directory of useful decoy-enhanced (DUD-E) and 84 structures from the Gunasekaran dataset. Our results show successful refinement of apo binding-site structures toward holo conformations in 82% of the test cases. In addition, virtual screenin

SUBMITTER: Guterres H 

PROVIDER: S-EPMC7856192 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature