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Calculations of Absolute Solvation Free Energies with Transformato—Application to the FreeSolv Database Using the CGenFF Force Field

[Image: see text] We recently introduced transformato, an open-source Python package for the automated setup of large-scale calculations of relative solvation and binding free energy differences. Here, we extend the capabilities of transformato to the calculation of absolute solvation free energy di...

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Autores principales: Karwounopoulos, Johannes, Kaupang, Åsmund, Wieder, Marcus, Boresch, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10500982/
https://www.ncbi.nlm.nih.gov/pubmed/37616333
http://dx.doi.org/10.1021/acs.jctc.3c00691
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author Karwounopoulos, Johannes
Kaupang, Åsmund
Wieder, Marcus
Boresch, Stefan
author_facet Karwounopoulos, Johannes
Kaupang, Åsmund
Wieder, Marcus
Boresch, Stefan
author_sort Karwounopoulos, Johannes
collection PubMed
description [Image: see text] We recently introduced transformato, an open-source Python package for the automated setup of large-scale calculations of relative solvation and binding free energy differences. Here, we extend the capabilities of transformato to the calculation of absolute solvation free energy differences. After careful validation against the literature results and reference calculations with the PERT module of CHARMM, we used transformato to compute absolute solvation free energies for most molecules in the FreeSolv database (621 out of 642). The force field parameters were obtained with the program cgenff (v2.5.1), which derives missing parameters from the CHARMM general force field (CGenFF v4.6). A long-range correction for the Lennard-Jones interactions was added to all computed solvation free energies. The mean absolute error compared to the experimental data is 1.12 kcal/mol. Our results allow a detailed comparison between the AMBER and CHARMM general force fields and provide a more in-depth understanding of the capabilities and limitations of the CGenFF small molecule parameters.
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spelling pubmed-105009822023-09-15 Calculations of Absolute Solvation Free Energies with Transformato—Application to the FreeSolv Database Using the CGenFF Force Field Karwounopoulos, Johannes Kaupang, Åsmund Wieder, Marcus Boresch, Stefan J Chem Theory Comput [Image: see text] We recently introduced transformato, an open-source Python package for the automated setup of large-scale calculations of relative solvation and binding free energy differences. Here, we extend the capabilities of transformato to the calculation of absolute solvation free energy differences. After careful validation against the literature results and reference calculations with the PERT module of CHARMM, we used transformato to compute absolute solvation free energies for most molecules in the FreeSolv database (621 out of 642). The force field parameters were obtained with the program cgenff (v2.5.1), which derives missing parameters from the CHARMM general force field (CGenFF v4.6). A long-range correction for the Lennard-Jones interactions was added to all computed solvation free energies. The mean absolute error compared to the experimental data is 1.12 kcal/mol. Our results allow a detailed comparison between the AMBER and CHARMM general force fields and provide a more in-depth understanding of the capabilities and limitations of the CGenFF small molecule parameters. American Chemical Society 2023-08-24 /pmc/articles/PMC10500982/ /pubmed/37616333 http://dx.doi.org/10.1021/acs.jctc.3c00691 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/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/).
spellingShingle Karwounopoulos, Johannes
Kaupang, Åsmund
Wieder, Marcus
Boresch, Stefan
Calculations of Absolute Solvation Free Energies with Transformato—Application to the FreeSolv Database Using the CGenFF Force Field
title Calculations of Absolute Solvation Free Energies with Transformato—Application to the FreeSolv Database Using the CGenFF Force Field
title_full Calculations of Absolute Solvation Free Energies with Transformato—Application to the FreeSolv Database Using the CGenFF Force Field
title_fullStr Calculations of Absolute Solvation Free Energies with Transformato—Application to the FreeSolv Database Using the CGenFF Force Field
title_full_unstemmed Calculations of Absolute Solvation Free Energies with Transformato—Application to the FreeSolv Database Using the CGenFF Force Field
title_short Calculations of Absolute Solvation Free Energies with Transformato—Application to the FreeSolv Database Using the CGenFF Force Field
title_sort calculations of absolute solvation free energies with transformato—application to the freesolv database using the cgenff force field
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10500982/
https://www.ncbi.nlm.nih.gov/pubmed/37616333
http://dx.doi.org/10.1021/acs.jctc.3c00691
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