Learning about Biomolecular Solvation from Water in Protein Crystals.

dc.contributor.author

Altan, Irem

dc.contributor.author

Fusco, Diana

dc.contributor.author

Afonine, Pavel V

dc.contributor.author

Charbonneau, Patrick

dc.date.accessioned

2022-05-02T17:31:38Z

dc.date.available

2022-05-02T17:31:38Z

dc.date.issued

2018-03

dc.date.updated

2022-05-02T17:31:38Z

dc.description.abstract

Water occupies typically 50% of a protein crystal and thus significantly contributes to the diffraction signal in crystallography experiments. Separating its contribution from that of the protein is, however, challenging because most water molecules are not localized and are thus difficult to assign to specific density peaks. The intricateness of the protein-water interface compounds this difficulty. This information has, therefore, not often been used to study biomolecular solvation. Here, we develop a methodology to surmount in part this difficulty. More specifically, we compare the solvent structure obtained from diffraction data for which experimental phasing is available to that obtained from constrained molecular dynamics (MD) simulations. The resulting spatial density maps show that commonly used MD water models are only partially successful at reproducing the structural features of biomolecular solvation. The radial distribution of water is captured with only slightly higher accuracy than its angular distribution, and only a fraction of the water molecules assigned with high reliability to the crystal structure is recovered. These differences are likely due to shortcomings of both the water models and the protein force fields. Despite these limitations, we manage to infer protonation states of some of the side chains utilizing MD-derived densities.

dc.identifier.issn

1520-6106

dc.identifier.issn

1520-5207

dc.identifier.uri

https://hdl.handle.net/10161/24993

dc.language

eng

dc.publisher

American Chemical Society (ACS)

dc.relation.ispartof

The journal of physical chemistry. B

dc.relation.isversionof

10.1021/acs.jpcb.7b09898

dc.subject

Water

dc.subject

Mannose-Binding Lectin

dc.subject

Crystallization

dc.subject

Solubility

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Thermodynamics

dc.subject

Molecular Dynamics Simulation

dc.title

Learning about Biomolecular Solvation from Water in Protein Crystals.

dc.type

Journal article

duke.contributor.orcid

Charbonneau, Patrick|0000-0001-7174-0821

pubs.begin-page

2475

pubs.end-page

2486

pubs.issue

9

pubs.organisational-group

Duke

pubs.organisational-group

Trinity College of Arts & Sciences

pubs.organisational-group

Chemistry

pubs.organisational-group

Physics

pubs.publication-status

Published

pubs.volume

122

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