6
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Perturbation Free-Energy Toolkit: An Automated Alchemical Topology Builder

      research-article
      Journal of Chemical Information and Modeling
      American Chemical Society

      Read this article at

      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.

          Abstract

          Free-energy calculations play an important role in the application of computational chemistry to a range of fields, including protein biochemistry, rational drug design, or materials science. Importantly, the free-energy difference is directly related to experimentally measurable quantities such as partition and adsorption coefficients, water activity, and binding affinities. Among several techniques aimed at predicting free-energy differences, perturbation approaches, involving the alchemical transformation of one molecule into another through intermediate states, stand out as rigorous methods based on statistical mechanics. However, despite the importance of free-energy calculations, the applicability of the perturbation approaches is still largely impeded by a number of challenges, including the definition of the perturbation path, i.e., alchemical changes leading to the transformation of one molecule to the other. To address this, an automatic perturbation topology builder based on a graph-matching algorithm is developed, which can identify the maximum common substructure (MCS) of two or multiple molecules and provide the perturbation topologies suitable for free-energy calculations using the GROMOS and the GROMACS simulation packages. Various MCS search options are presented leading to alternative definitions of the perturbation pathway. Moreover, perturbation topologies generated using the default multistate MCS search are used to calculate the changes in free energy between lysine and its two post-translational modifications, 3-methyllysine and acetyllysine. The pairwise free-energy calculations performed on this test system led to a cycle closure of 0.5 ± 0.3 and 0.2 ± 0.2 kJ mol –1, with GROMOS and GROMACS simulation packages, respectively. The same relative free energies between the three states are obtained by employing the enveloping distribution sampling (EDS) approach when compared to the pairwise perturbations. Importantly, this toolkit is made available online as an open-source Python package ( https://github.com/drazen-petrov/SMArt).

          Related collections

          Most cited references64

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

          GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers

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

            Molecular dynamics with coupling to an external bath

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

              LINCS: A linear constraint solver for molecular simulations

                Bookmark

                Author and article information

                Journal
                J Chem Inf Model
                J Chem Inf Model
                ci
                jcisd8
                Journal of Chemical Information and Modeling
                American Chemical Society
                1549-9596
                1549-960X
                20 August 2021
                27 September 2021
                : 61
                : 9
                : 4382-4390
                Affiliations
                [1]Department of Material Sciences and Process Engineering, Institute of Molecular Modeling and Simulation, University of Natural Resources and Life Sciences Vienna , Muthgasse 18, A-1190 Vienna, Austria
                Author notes
                Author information
                https://orcid.org/0000-0001-6221-7369
                Article
                10.1021/acs.jcim.1c00428
                8479811
                34415755
                c4cf06a1-dd16-46ab-a836-08dfb7fece3a
                © 2021 The Author. Published by American Chemical Society

                Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 15 April 2021
                Funding
                Funded by: Peter und Traudl Engelhorn Stiftung, doi 10.13039/501100014381;
                Award ID: NA
                Categories
                Article
                Custom metadata
                ci1c00428
                ci1c00428

                Computational chemistry & Modeling
                Computational chemistry & Modeling

                Comments

                Comment on this article