Sampling of conformational ensemble for virtual screening using molecular dynamics simulations and normal mode analysis

Gautier Moroy, Olivier Sperandio, Shakti Rielland, Saurabh Khemka, Karen Druart, Divij Goyal, David Perahia, Maria A Miteva
2015 Future Medicinal Chemistry  
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,
more » ... ate 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.
doi:10.4155/fmc.15.150 pmid:26599419 fatcat:f23jonpdnrbzfknpz4djvbytvi