Computation of protein–ligand binding free energies using quantum mechanical bespoke force fields† †The authors are grateful to Alice Allen (ORCID: 0000-0002-8727-8333) and Joshua Horton (ORCID: 0000-0001-8694-7200) for helpful discussions, and to the EPSRC (EP/R010153/1) and the National Institutes of Health (GM32136) for funding. This research made use of the Rocket High Performance Computing Service at Newcastle University. ‡ ‡Electronic supplementary information (ESI) available: Computationa

Computation of protein–ligand binding free energies using quantum mechanical bespoke force fields† †The authors are grateful to Alice Allen (ORCID: 0000-0002-8727-8333) and Joshua Horton (ORCID: 0000-0001-8694-7200) for helpful discussions, and to the EPSRC (EP/R010153/1) and the National Institutes of Health (GM32136) for funding. This research made use of the Rocket High Performance Computing Service at Newcastle University. ‡ ‡Electronic supplementary information (ESI) available: Computationa

A quantum mechanical bespoke molecular mechanics force field is derived for the L99A mutant of T4 lysozyme and used to compute absolute binding free energies of six benzene analogs to the protein. A quantum mechanical bespoke molecular mechanics force field is derived for the L99A mutant of T4 lysoz...

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Bibliographic Details
Published in:MedChemComm 2019-02, Vol.10 (7), p.1116-1120
Main Authors: Cole, Daniel J., Cabeza de Vaca, Israel, Jorgensen, William L.
Format: Article
Language:eng
Subjects:
Chemistry
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Summary:A quantum mechanical bespoke molecular mechanics force field is derived for the L99A mutant of T4 lysozyme and used to compute absolute binding free energies of six benzene analogs to the protein. A quantum mechanical bespoke molecular mechanics force field is derived for the L99A mutant of T4 lysozyme and used to compute absolute binding free energies of six benzene analogs to the protein. Promising agreement between theory and experiment highlights the potential for future use of system-specific force fields in computer-aided drug design.
ISSN:2040-2503
2040-2511