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Comparison of grand canonical and conventional molecular dynamics simulation methods for protein-bound water networks

Comparison of grand canonical and conventional molecular dynamics simulation methods for protein-bound water networks
Comparison of grand canonical and conventional molecular dynamics simulation methods for protein-bound water networks
Water molecules play important roles in all biochemical processes. Therefore, it is of key importance to obtain information of the structure, dynamics, and thermodynamics of water molecules around proteins. Numerous computational methods have been suggested with this aim. In this study, we compare the performance of conventional and grand-canonical Monte Carlo (GCMC) molecular dynamics (MD) simulations to sample the water structure, as well GCMC and grid-based inhomogeneous solvation theory (GIST) to describe the energetics of the water network. They are evaluated on two proteins: the buried ligand-binding site of a ferritin dimer and the solvent-exposed binding site of galectin-3. We show that GCMC/MD simulations significantly speed up the sampling and equilibration of water molecules in the buried binding site, thereby making the results more similar for simulations started from different states. Both GCMC/MD and conventional MD reproduce crystal-water molecules reasonably for the buried binding site. GIST analyses are normally based on restrained MD simulations. This improves the precision of the calculated energies, but the restraints also significantly affect both absolute and relative energies. Solvation free energies for individual water molecules calculated with and without restraints show a good correlation, but with large quantitative differences. Finally, we note that the solvation free energies calculated with GIST are ∼5 times larger than those estimated by GCMC owing to differences in the reference state.
protein solvation, Water networks, molecular dynamics simulations, grand-cannonical Monte-Carlo simulations, grid-based inhomogeneous solvation theory
2694-2445
247-259
Ekberg, Vilhelm
8621c1e4-1d03-4683-8694-6361dea67939
Samways, Marley, Luke
75cda5aa-31ef-4f62-9ea3-8655ea55d3fb
Misini Ignjatovic, Majda
69c8225e-9948-4d83-9eb3-b50544f8dbbc
Essex, Jonathan W.
1f409cfe-6ba4-42e2-a0ab-a931826314b5
Ryde, Ulf
75de3776-4811-4e3c-96a7-9e23058cd213
Ekberg, Vilhelm
8621c1e4-1d03-4683-8694-6361dea67939
Samways, Marley, Luke
75cda5aa-31ef-4f62-9ea3-8655ea55d3fb
Misini Ignjatovic, Majda
69c8225e-9948-4d83-9eb3-b50544f8dbbc
Essex, Jonathan W.
1f409cfe-6ba4-42e2-a0ab-a931826314b5
Ryde, Ulf
75de3776-4811-4e3c-96a7-9e23058cd213

Ekberg, Vilhelm, Samways, Marley, Luke, Misini Ignjatovic, Majda, Essex, Jonathan W. and Ryde, Ulf (2022) Comparison of grand canonical and conventional molecular dynamics simulation methods for protein-bound water networks. ACS Physical Chemistry Au, 2 (3), 247-259. (doi:10.1021/acsphyschemau.1c00052).

Record type: Article

Abstract

Water molecules play important roles in all biochemical processes. Therefore, it is of key importance to obtain information of the structure, dynamics, and thermodynamics of water molecules around proteins. Numerous computational methods have been suggested with this aim. In this study, we compare the performance of conventional and grand-canonical Monte Carlo (GCMC) molecular dynamics (MD) simulations to sample the water structure, as well GCMC and grid-based inhomogeneous solvation theory (GIST) to describe the energetics of the water network. They are evaluated on two proteins: the buried ligand-binding site of a ferritin dimer and the solvent-exposed binding site of galectin-3. We show that GCMC/MD simulations significantly speed up the sampling and equilibration of water molecules in the buried binding site, thereby making the results more similar for simulations started from different states. Both GCMC/MD and conventional MD reproduce crystal-water molecules reasonably for the buried binding site. GIST analyses are normally based on restrained MD simulations. This improves the precision of the calculated energies, but the restraints also significantly affect both absolute and relative energies. Solvation free energies for individual water molecules calculated with and without restraints show a good correlation, but with large quantitative differences. Finally, we note that the solvation free energies calculated with GIST are ∼5 times larger than those estimated by GCMC owing to differences in the reference state.

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More information

Accepted/In Press date: 28 January 2022
e-pub ahead of print date: 11 February 2022
Published date: 25 May 2022
Additional Information: © 2022 The Authors. Published by American Chemical Society.
Keywords: protein solvation, Water networks, molecular dynamics simulations, grand-cannonical Monte-Carlo simulations, grid-based inhomogeneous solvation theory

Identifiers

Local EPrints ID: 456376
URI: http://eprints.soton.ac.uk/id/eprint/456376
ISSN: 2694-2445
PURE UUID: 04790ac2-2c81-4e1b-a41e-0cbc768f5874
ORCID for Marley, Luke Samways: ORCID iD orcid.org/0000-0001-9431-8789
ORCID for Jonathan W. Essex: ORCID iD orcid.org/0000-0003-2639-2746

Catalogue record

Date deposited: 27 Apr 2022 15:22
Last modified: 23 Sep 2022 01:33

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Contributors

Author: Vilhelm Ekberg
Author: Marley, Luke Samways ORCID iD
Author: Majda Misini Ignjatovic
Author: Ulf Ryde

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