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Water structure in solution and crystal molecular dynamics simulations compared to protein crystal structures

Caldararu, Octav LU ; Misini Ignjatovic, Majda LU ; Oksanen, Esko LU and Ryde, Ulf LU (2020) In RSC Advances 10. p.8435-8443
Abstract
The function of proteins is influenced not only by the atomic structure but also by the detailed structure of the solvent surrounding it. Computational studies of protein structure also critically depend on the water structure around the protein. Herein we compare the water structure obtained from molecular dynamics (MD) simulations of galectin-3 in complex with two ligands to crystallographic water molecules observed in the corresponding crystal structures. We computed MD trajectories both in a water box, which mimics a protein in solution, and in a crystallographic unit cell, which mimics a protein in a crystal. The calculations were compared to crystal structures obtained at both cryogenic and room temperature. Two types of analyses of... (More)
The function of proteins is influenced not only by the atomic structure but also by the detailed structure of the solvent surrounding it. Computational studies of protein structure also critically depend on the water structure around the protein. Herein we compare the water structure obtained from molecular dynamics (MD) simulations of galectin-3 in complex with two ligands to crystallographic water molecules observed in the corresponding crystal structures. We computed MD trajectories both in a water box, which mimics a protein in solution, and in a crystallographic unit cell, which mimics a protein in a crystal. The calculations were compared to crystal structures obtained at both cryogenic and room temperature. Two types of analyses of the MD simulations were performed. First, the positions of the crystallographic water molecules were compared to peaks in the MD density after alignment of the protein in each snapshot. The results of this analysis indicate that all simulations reproduce the crystallographic water structure rather poorly. However, if we define the crystallographic water sites based on their distances to nearby protein atoms and follow these sites throughout the simulations, the MD simulations reproduce the crystallographic water sites much better. This shows that the failure of MD simulations to reproduce the water structure around proteins in crystal structures observed both in this and previous studies is caused by the problem of identifying water sites for a flexible and dynamic protein (traditionally done by overlaying the structures). Our local clustering approach solves the problem and shows that the MD simulations reasonably reproduce the water structure observed in crystals. Furthermore, analysis of the crystal MD simulations indicates a few water molecules that are close to unmodeled electron density peaks in the crystal structures, suggesting that crystal MD could be used as a complementary tool for identifying and modelling water in protein crystallography. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
in
RSC Advances
volume
10
pages
8435 - 8443
publisher
Royal Society of Chemistry
external identifiers
  • scopus:85081121460
ISSN
2046-2069
DOI
10.1039/c9ra09601a
language
English
LU publication?
yes
id
de76e44e-9b87-4295-886e-826519adfefb
date added to LUP
2020-09-26 10:35:51
date last changed
2020-10-04 08:05:35
@article{de76e44e-9b87-4295-886e-826519adfefb,
  abstract     = {The function of proteins is influenced not only by the atomic structure but also by the detailed structure of the solvent surrounding it. Computational studies of protein structure also critically depend on the water structure around the protein. Herein we compare the water structure obtained from molecular dynamics (MD) simulations of galectin-3 in complex with two ligands to crystallographic water molecules observed in the corresponding crystal structures. We computed MD trajectories both in a water box, which mimics a protein in solution, and in a crystallographic unit cell, which mimics a protein in a crystal. The calculations were compared to crystal structures obtained at both cryogenic and room temperature. Two types of analyses of the MD simulations were performed. First, the positions of the crystallographic water molecules were compared to peaks in the MD density after alignment of the protein in each snapshot. The results of this analysis indicate that all simulations reproduce the crystallographic water structure rather poorly. However, if we define the crystallographic water sites based on their distances to nearby protein atoms and follow these sites throughout the simulations, the MD simulations reproduce the crystallographic water sites much better. This shows that the failure of MD simulations to reproduce the water structure around proteins in crystal structures observed both in this and previous studies is caused by the problem of identifying water sites for a flexible and dynamic protein (traditionally done by overlaying the structures). Our local clustering approach solves the problem and shows that the MD simulations reasonably reproduce the water structure observed in crystals. Furthermore, analysis of the crystal MD simulations indicates a few water molecules that are close to unmodeled electron density peaks in the crystal structures, suggesting that crystal MD could be used as a complementary tool for identifying and modelling water in protein crystallography.},
  author       = {Caldararu, Octav and Misini Ignjatovic, Majda and Oksanen, Esko and Ryde, Ulf},
  issn         = {2046-2069},
  language     = {eng},
  month        = {02},
  pages        = {8435--8443},
  publisher    = {Royal Society of Chemistry},
  series       = {RSC Advances},
  title        = {Water structure in solution and crystal molecular dynamics simulations compared to protein crystal structures},
  url          = {https://lup.lub.lu.se/search/ws/files/84188207/water_md_cryst_264.pdf},
  doi          = {10.1039/c9ra09601a},
  volume       = {10},
  year         = {2020},
}