Simulations of macromolecules in protective and denaturing osmolytes: properties of mixed solvent systems and their effects on water and protein structure and dynamics.

Simulations of macromolecules in protective and denaturing osmolytes: properties of mixed solvent systems and their effects on water and protein structure and dynamics. Research Abstract Details 

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Simulations of macromolecules in protective and denaturing osmolytes: properties of mixed solvent systems and their effects on water and protein structure and dynamics. Abstract Text:

David A C Beck,Brian J Bennion,Darwin O V Alonso,Valerie Daggett,

Rarely is any solution simply solute and water. In vivo, solutes, such as proteins and nucleic acids, swim in a sea of water, salts, ions, small molecules, and lipids, not to mention other macromolecules. In vitro, virtually all solutions contain a mixture of aqueous solvents, or "cosolvents" [i.e., solvent(s) in addition to water], that can alter the dynamics, behavior, solubility, and stability of proteins and nucleic acids. We have developed models for a number of cosolvents, including the denaturant urea and the small chemical chaperone trimethylamine N-oxide (TMAO). This chapter examines the models for these two cosolvents in the context of experimental data. The direct and indirect effects of these molecules on water and protein are studied with molecular dynamics simulations. These observations and conclusions are drawn from simulations of these molecules in pure water and as a cosolvent for the protein chymotrypsin inhibitor 2. Urea-induced denaturation occurs initially through attack of the protein by water and hydration of hydrophobic protein moieties as a result of disruption of the hydrogen bonding network of water by urea. This indirect denaturing effect of urea is followed by more direct action as urea replaces some waters involved in the initial hydration of the hydrophobic core and subsequently binds to polar residues and the protein main chain to compete with the intraprotein hydrogen bonds. In the case of TMAO, we find that it encourages water-water interactions, thereby stabilizing the protein as a result of the increased penalty for the hydration of hydrophobic residues.

Simulations of macromolecules in protective and denaturing osmolytes: properties of mixed solvent systems and their effects on water and protein structure and dynamics. Publishing Authors By Initials

DA Beck,BJ Bennion,DO Alonso,V Daggett,

For similar water research abstracts see: water research

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Simulations of macromolecules in protective and denaturing osmolytes: properties of mixed solvent systems and their effects on water and protein structure and dynamics. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Methods in enzymology

VOLUME: 428

Page Numbers: 373-96

Journal Abbreviation: Meth. Enzymol.

ISSN: 0076-6879

DAY: 3

MONTH: 12

YEAR: 2007

Simulations of macromolecules in protective and denaturing osmolytes: properties of mixed solvent systems and their effects on water and protein structure and dynamics. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 212271

Simulations of macromolecules in protective and denaturing osmolytes: properties of mixed solvent systems and their effects on water and protein structure and dynamics. Keywords Mesh Terms:

KEYWORDS: Water

MESH TERMS: chemistry

Chemical & Substance for Abstract: Simulations of macromolecules in protective and denaturing osmolytes: properties of mixed solvent systems and their effects on water and protein structure and dynamics. Information

Substance Name: Water

Registry Number: 7732-18-5

Grant and Affiliation Information for Simulations of macromolecules in protective and denaturing osmolytes: properties of mixed solvent systems and their effects on water and protein structure and dynamics.

AFFILIATION: Department of Medicinal Chemistry, University of Washington, Seattle, Washington, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM50789

ACRONYM: GM

MEDLINETA: Methods Enzymol

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