Predicting fragment binding modes using customized Lennard-Jones potentials in short molecular dynamics simulations.

ABSTRACT: Reliable in silico prediction of fragment binding modes remains a challenge in current drug design research. Due to their small size and generally low binding affinity, fragments can potentially interact with their target proteins in different ways. In the current study, we propose a workflow aimed at predicting favorable fragment binding sites and binding poses through multiple short molecular dynamics simulations. Tailored Lennard-Jones potentials enable the simulation of systems with high concentrations of identical fragment molecules surrounding their respective target proteins. In the present study, descriptors and binding free energy calculations were implemented to filter out the desired fragment position. The proposed method was tested for its performance using four epigenetic targ

SUBMITTER: Vorreiter C 

PROVIDER: S-EPMC11733276 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature