6
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      Efficient sampling of puckering states of monosaccharides through replica exchange with solute tempering and bond softening

      1 , 2 , 2
      The Journal of Chemical Physics
      AIP Publishing

      Read this article at

      ScienceOpenPublisher
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Related collections

          Most cited references31

          • Record: found
          • Abstract: not found
          • Article: not found

          Replica Monte Carlo Simulation of Spin-Glasses

            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Accurate and reliable prediction of relative ligand binding potency in prospective drug discovery by way of a modern free-energy calculation protocol and force field.

            Designing tight-binding ligands is a primary objective of small-molecule drug discovery. Over the past few decades, free-energy calculations have benefited from improved force fields and sampling algorithms, as well as the advent of low-cost parallel computing. However, it has proven to be challenging to reliably achieve the level of accuracy that would be needed to guide lead optimization (∼5× in binding affinity) for a wide range of ligands and protein targets. Not surprisingly, widespread commercial application of free-energy simulations has been limited due to the lack of large-scale validation coupled with the technical challenges traditionally associated with running these types of calculations. Here, we report an approach that achieves an unprecedented level of accuracy across a broad range of target classes and ligands, with retrospective results encompassing 200 ligands and a wide variety of chemical perturbations, many of which involve significant changes in ligand chemical structures. In addition, we have applied the method in prospective drug discovery projects and found a significant improvement in the quality of the compounds synthesized that have been predicted to be potent. Compounds predicted to be potent by this approach have a substantial reduction in false positives relative to compounds synthesized on the basis of other computational or medicinal chemistry approaches. Furthermore, the results are consistent with those obtained from our retrospective studies, demonstrating the robustness and broad range of applicability of this approach, which can be used to drive decisions in lead optimization.
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              General definition of ring puckering coordinates

                Bookmark

                Author and article information

                Journal
                The Journal of Chemical Physics
                The Journal of Chemical Physics
                AIP Publishing
                0021-9606
                1089-7690
                August 21 2018
                August 21 2018
                : 149
                : 7
                : 072306
                Affiliations
                [1 ]Schrödinger, Inc., 120 West 45th Street, New York, New York 10036, USA
                [2 ]Department of Chemistry, Columbia University, 3000 Broadway, New York, New York 10027, USA
                Article
                10.1063/1.5024389
                9f8eb19f-b34c-43ff-8377-7fbb54772728
                © 2018
                History

                Comments

                Comment on this article