Journal ArticleDOI
Effects of urea, tetramethyl urea, and trimethylamine N-oxide on aqueous solution structure and solvation of protein backbones: a molecular dynamics simulation study.
Haiyan Wei,Yubo Fan,Yi Qin Gao +2 more
TLDR
Simulation results reveal the potential importance of the indirect effects of cosolvents in protein denaturation or structure protection, particularly through modifying of the water-amide interactions.Abstract:
The effects of urea, tetramethyl urea (TMU), and trimethylamine N-oxide (TMAO) on the structure and dynamics of aqueous solutions are studied using molecular dynamics simulations. It was found that urea has little effects on the water−water hydrogen-bond length and angle distributions except that it induces a slight collapse of the second shell in the hydrogen-bonding network. TMU and TMAO both strengthen the individual hydrogen bonds and significantly slow the orientational relaxation of water, but have opposite effects on the second shell structure of the hydrogen-bonding network: TMU distorts while TMAO enhances the tetrahedral water structure. Furthermore, TMAO significantly weakens the interactions between the amide carbonyl group and the water molecules, while TMU and urea both strengthen these interactions, with the effect of urea being much less significant than that of TMU. These conclusions are supported by molecular dynamics simulations of three different systems: a model amide compound CH3−NH−...read more
Citations
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Protein–excipient interactions: Mechanisms and biophysical characterization applied to protein formulation development
TL;DR: Key mechanisms of protein-excipient interactions such as electrostatic and cation-pi interactions, preferential hydration, dispersive forces, and hydrogen bonding are presented in the context of different physical states of the formulation.
Journal ArticleDOI
Microscopic insights into the protein-stabilizing effect of trimethylamine N-oxide (TMAO).
TL;DR: An infrared experiment designed to probe the microscopic details of this action explicitly from the perspective of the solute molecule reveals that the protein-stabilizing effect of TMAO originates from two contributions: One is entropic and the other is enthalpic in nature.
Journal ArticleDOI
A Simple Theory for the Hofmeister Series
Wen Jun Xie,Yi Qin Gao +1 more
TL;DR: A simple and self-consistent theory that takes into account the cooperative effects of cations and anions in affecting water/air surface tension, water activity, and the solubility of model compounds including polypeptides is discussed.
Journal ArticleDOI
Molecular mechanism for the preferential exclusion of TMAO from protein surfaces.
TL;DR: An all-atom molecular model is developed that captures the exclusion of TMAO from model compounds and protein surfaces, as a consequence of incorporating realistic T MAO-water interactions through osmotic pressure measurements, and suggests a general principle for preferential interaction behavior of cosolvents with protein surfaces.
Journal ArticleDOI
How a protein can remain stable in a solvent with high content of urea: insights from molecular dynamics simulation of Candida antarctica lipase B in urea : choline chloride deep eutectic solvent
Hassan Monhemi,Mohammad Reza Housaindokht,Ali Akbar Moosavi-Movahedi,Mohammad Reza Bozorgmehr +3 more
TL;DR: This is the first study in which the microstructural properties of a macromolecule are examined in a deep eutectic solvent and it was found that urea molecules denature the enzyme by interrupting the intra-chain hydrogen bonds in a "direct denaturation mechanism".
References
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Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems
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Numerical Integration of the Cartesian Equations of Motion of a System with Constraints: Molecular Dynamics of n-Alkanes
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A New Mixing of Hartree-Fock and Local Density-Functional Theories
TL;DR: In this article, a new coupling of Hartree-Fock theory with local density functional theory was proposed to improve the predictive power of the Hartree−Fock model for molecular bonding, and the results of tests on atomization energies, ionization potentials, and proton affinities were reported.