Ligand-Enhanced Negative Images Optimized for Docking Rescoring.

ABSTRACT: Despite the pivotal role of molecular docking in modern drug discovery, the default docking scoring functions often fail to recognize active ligands in virtual screening campaigns. Negative image-based rescoring improves docking enrichment by comparing the shape/electrostatic potential (ESP) of the flexible docking poses against the target protein's inverted cavity volume. By optimizing these negative image-based (NIB) models using a greedy search, the docking rescoring yield can be improved massively and consistently. Here, a fundamental modification is implemented to this shape-focused pharmacophore modelling approach-actual ligand 3D coordinates are incorporated into the NIB models for the optimization. This hybrid approach, labelled as ligand-enhanced brute-force negative image-based o

SUBMITTER: Kurkinen ST 

PROVIDER: S-EPMC9323918 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature