2 research outputs found
Sampling of conformational ensemble for virtual screening using molecular dynamics simulations and normal mode analysis
Aim: Molecular dynamics simulations and normal mode analysis are
well-established approaches to generate receptor conformational ensembles
(RCEs) for ligand docking and virtual screening. Here, we report new fast
molecular dynamics-based and normal mode analysis-based protocols combined with
conformational pocket classifications to efficiently generate RCEs. Materials
\& methods: We assessed our protocols on two well-characterized protein targets
showing local active site flexibility, dihydrofolate reductase and large
collective movements, CDK2. The performance of the RCEs was validated by
distinguishing known ligands of dihydrofolate reductase and CDK2 among a
dataset of diverse chemical decoys. Results \& discussion: Our results show
that different simulation protocols can be efficient for generation of RCEs
depending on different kind of protein flexibility