Comparison of Grand Canonical and Conventional Molecular Dynamics Simulation Methods for Protein-Bound Water Networks
(2022) In ACS Physical Chemistry Au 2(3). p.247-259- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/df065074-5214-41f0-a9b3-3ea2f4a2fdf6
- author
- Ekberg, Vilhelm
LU
; L. Samways, Marley
; Misini Ignjatović, Majda
LU
; W. Essex, Jonathan
and Ryde, Ulf
LU
- organization
- publishing date
- 2022
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- protein solvation, water networks, molecular dynamics simulations, grand-canonical Monte Carlo simulations, grid-based inhomogeneous solvation theory
- in
- ACS Physical Chemistry Au
- volume
- 2
- issue
- 3
- pages
- 13 pages
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- pmid:35637786
- scopus:85146064830
- ISSN
- 2694-2445
- DOI
- 10.1021/acsphyschemau.1c00052
- language
- English
- LU publication?
- yes
- id
- df065074-5214-41f0-a9b3-3ea2f4a2fdf6
- date added to LUP
- 2022-11-30 09:16:34
- date last changed
- 2023-04-11 07:29:05
@article{df065074-5214-41f0-a9b3-3ea2f4a2fdf6, 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.}}, author = {{Ekberg, Vilhelm and L. Samways, Marley and Misini Ignjatović, Majda and W. Essex, Jonathan and Ryde, Ulf}}, issn = {{2694-2445}}, keywords = {{protein solvation; water networks; molecular dynamics simulations; grand-canonical Monte Carlo simulations; grid-based inhomogeneous solvation theory}}, language = {{eng}}, number = {{3}}, pages = {{247--259}}, publisher = {{The American Chemical Society (ACS)}}, series = {{ACS Physical Chemistry Au}}, title = {{Comparison of Grand Canonical and Conventional Molecular Dynamics Simulation Methods for Protein-Bound Water Networks}}, url = {{http://dx.doi.org/10.1021/acsphyschemau.1c00052}}, doi = {{10.1021/acsphyschemau.1c00052}}, volume = {{2}}, year = {{2022}}, }