title: Driving Structure-Based Drug Discovery through Cosolvent Molecular Dynamics.
abstract: Identifying binding hotspots on protein surfaces is of prime interest in structure-based drug discovery, either to assess the tractability of pursuing a protein target or to drive improved potency of lead compounds. Computational approaches to detect such regions have traditionally relied on energy minimization of probe molecules onto static protein conformations in the absence of the natural aqueous environment. Advances in high performance computing now allow us to assess hotspots using molecular dynamics (MD) simulations. MD simulations integrate protein flexibility and the complicated role of water, thereby providing a more realistic assessment of the complex kinetics and thermodynamics at play. In this review, we describe the evolution of various cosolvent-based MD techniques and highlight a myriad of potential applications for such technologies in computational drug development.
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Michigan , 428 Church Street, Ann Arbor, Michigan 48109-1065, United States.
authors.forename: Phani
authors.initials: P
authors.lastname: Ghanakota
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Michigan , 428 Church Street, Ann Arbor, Michigan 48109-1065, United States.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Carlson
mesh_terms: D055808:Drug Discovery; D056004:Molecular Dynamics Simulation