title: Parallelized-over-parts computation of absolute binding free energy with docking and molecular dynamics.
abstract: We present a technique for biomolecular free energy calculations that exploits highly parallelized sampling to significantly reduce the time to results. The technique combines free energies for multiple, nonoverlapping configurational macrostates and is naturally suited to distributed computing. We describe a methodology that uses this technique with docking, molecular dynamics, and free energy perturbation to compute absolute free energies of binding quickly compared to previous methods. The method does not require a priori knowledge of the binding pose as long as the docking technique used can generate reasonable binding modes. We demonstrate the method on the protein FKBP12 and eight of its inhibitors.
authors.affiliation: Computer Science Department, Stanford University, Stanford, CA 94305, USA.
authors.forename: Guha
authors.initials: G
authors.lastname: Jayachandran
authors.forename: Michael R
authors.initials: MR
authors.lastname: Shirts
authors.forename: Sanghyun
authors.initials: S
authors.lastname: Park
authors.forename: Vijay S
authors.initials: VS
authors.lastname: Pande
mesh_terms: D001703:Biophysics / Q000379:methods*; D002627:Chemistry, Physical / Q000379:methods; D016000:Cluster Analysis; D003198:Computer Simulation; D006801:Humans; D008024:Ligands; D008956:Models, Chemical; D015233:Models, Statistical; D008968:Molecular Conformation; D011336:Probability; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry*; D022061:Tacrolimus Binding Protein 1A / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D008024:Ligands; D011506:Proteins; D022061:Tacrolimus Binding Protein 1A