title: Sampling of conformational ensemble for virtual screening using molecular dynamics simulations and normal mode analysis.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Our results show that different simulation protocols can be efficient for generation of RCEs depending on different kind of protein flexibility.
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Molécules Thérapeutiques In Silico, INSERM UMR-S 973, Paris, France.|INSERM, U973, Paris, France.
authors.forename: Gautier
authors.initials: G
authors.lastname: Moroy
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Molécules Thérapeutiques In Silico, INSERM UMR-S 973, Paris, France.|INSERM, U973, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Sperandio
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Molécules Thérapeutiques In Silico, INSERM UMR-S 973, Paris, France.|INSERM, U973, Paris, France.
authors.forename: Shakti
authors.initials: S
authors.lastname: Rielland
authors.affiliation: Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), CNRS UMR 8113 ENS de Cachan, Cachan, France.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Khemka
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Molécules Thérapeutiques In Silico, INSERM UMR-S 973, Paris, France.|INSERM, U973, Paris, France.
authors.forename: Karen
authors.initials: K
authors.lastname: Druart
authors.affiliation: Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), CNRS UMR 8113 ENS de Cachan, Cachan, France.
authors.forename: Divij
authors.initials: D
authors.lastname: Goyal
authors.affiliation: Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), CNRS UMR 8113 ENS de Cachan, Cachan, France.
authors.forename: David
authors.initials: D
authors.lastname: Perahia
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Molécules Thérapeutiques In Silico, INSERM UMR-S 973, Paris, France.|INSERM, U973, Paris, France.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Miteva
mesh_terms: D001665:Binding Sites; D051357:Cyclin-Dependent Kinase 2 / Q000737:chemistry / Q000378:metabolism; D057166:High-Throughput Screening Assays; D006801:Humans; D008024:Ligands; D056004:Molecular Dynamics Simulation; D017434:Protein Structure, Tertiary; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry / Q000378:metabolism
chemical_list: D008024:Ligands; D013762:Tetrahydrofolate Dehydrogenase; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2
keywords: CDK2; DHFR; molecular dynamics simulations; normal mode analysis; protein conformational ensemble; virtual screening