title: Advances in free-energy-based simulations of protein folding and ligand binding.
abstract: Free-energy-based simulations are increasingly providing the narratives about the structures, dynamics and biological mechanisms that constitute the fabric of protein science. Here, we review two recent successes. It is becoming practical: first, to fold small proteins with free-energy methods without knowing substructures and second, to compute ligand-protein binding affinities, not just their binding poses. Over the past 40 years, the timescales that can be simulated by atomistic MD are doubling every 1.3 years--which is faster than Moore's law. Thus, these advances are not simply due to the availability of faster computers. Force fields, solvation models and simulation methodology have kept pace with computing advancements, and are now quite good. At the tip of the spear recently are GPU-based computing, improved fast-solvation methods, continued advances in force fields, and conformational sampling methods that harness external information.
authors.affiliation: Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, NY 11794, United States.
authors.forename: Alberto
authors.initials: A
authors.lastname: Perez
authors.affiliation: Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, NY 11794, United States.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Morrone
authors.affiliation: Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, NY 11794, United States; Department of Chemistry, Stony Brook University, Stony Brook, NY 11794, United States.
authors.forename: Carlos
authors.initials: C
authors.lastname: Simmerling
authors.affiliation: Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, NY 11794, United States; Department of Chemistry, Stony Brook University, Stony Brook, NY 11794, United States; Department of Physics and Astronomy, Stony Brook University, Stony Brook, NY 11794, United States. Electronic address: dill@laufercenter.org.
authors.forename: Ken A
authors.initials: KA
authors.lastname: Dill
mesh_terms: D006801:Humans; D008024:Ligands; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*
chemical_list: D008024:Ligands; D011506:Proteins