scholarly journals Transition-State Compressibility and Activation Volume of Transient Protein Conformational Fluctuations

JACS Au ◽  
2021 ◽  
Author(s):  
Matthias Dreydoppel ◽  
Britta Dorn ◽  
Kristofer Modig ◽  
Mikael Akke ◽  
Ulrich Weininger
1970 ◽  
Vol 48 (16) ◽  
pp. 2494-2499 ◽  
Author(s):  
Digby D. Macdonald ◽  
J. B. Hyne

First-order rate constants for the solvolysis of benzyl chloride in a series of aqueous acetone and aqueous dimethylsulfoxide (DMSO) mixtures at 50.100 °C and at various pressures in the range 1–4083 atm are reported. Volume of activation, calculated from the rate/pressure data, is found to exhibit extremum behavior with varying solvent composition in both solvent systems. The activation volumes are dissected into their initial state and transition state contributions by determining the "instantaneous" volumes of solution of benzyl chloride in the solvent systems. The contributions of both the initial state and the transition state to the behavior of the activation volume as a function of solvent composition are discussed.


2021 ◽  
Author(s):  
Samvel Avagyan ◽  
George Makhatadze

Hydrostatic pressure together with the temperature is an important environmental variable that plays an essential role in biological adaptation of extremophilic organisms. In particular, the effects of hy-drostatic pressure on the rates of the protein folding/unfolding reaction are determined by the magni-tude and sign of the activation volume changes. Here we provide computational description of the ac-tivation volume changes for folding/unfolding reaction, and compare them with the experimental data for six different globular proteins. We find that the volume of the transition state ensemble is always in-between the folded and unfolded states. Based on this, we conclude that hydrostatic pressure will invariably slow down protein folding and accelerate protein unfolding.


1970 ◽  
Vol 48 (13) ◽  
pp. 2025-2030 ◽  
Author(s):  
MOYRA J. Mackinnon ◽  
A. B. Lateef ◽  
J. B. Hyne

The transition state partial molal volume behavior, [Formula: see text] as a function of binary solvent composition was obtained for three reactions by dissection of the activation volume, ΔV*, into initial and transition state components: [Formula: see text] The solvolyses of t-butyl chloride, benzyl chloride, and p-chlorobenzyl chloride represented a gradation of reaction type between SN1 and SN2 and the transition state partial molal volume behavior was found to be distinctly different in each case and in agreement with the mechanistic classification of these reactions.


1990 ◽  
Vol 202 ◽  
Author(s):  
Michael J. Aziz ◽  
Paul C. Sabin ◽  
Guo-Quan Lu

ABSTRACTThe effect of nonhydrostatic stresses on the solid phase epitaxial growth rate of crystalline Si(100) into self-implanted amorphous surface layers has been measured. Uniaxial stresses of up to 6 kbar (0.6 GPa) were attained by bending wafers over SiO2 rods and annealing at a temperature too low for plastic deformation to relieve the stress in the crystal, but high enough for solid phase epitaxial growth to proceed. The growth rate on the tensile side was greater than that on the compressive side of the wafer, in marked contrast to the enhancement observed from hydrostatic pressure. The phenomenology of an “activation strain”, the nonhydrostatic analogue of the activation volume, has been developed to characterize the results. Combined with the measurement of the activation volume, the measurement reported here permits us to characterize to first order the entire activation strain tensor corresponding to the transition state for solid phase epitaxy of Si(lOO). We conclude that the transition state for this process is “short and fat”; that is, the fluctuation to the transition state involves an expansion in the two in-plane directions and a contraction in the direction normal to the surface large enough to make the overall volume change negative. The symmetry of the measured activation strain tensor is inconsistent with all bulk point defect mechanisms for solid phase epitaxy. The relevance of the activation strain formalism to heteroepitaxy and vapor phase epitaxy is discussed.


2003 ◽  
Vol 70 ◽  
pp. 213-220 ◽  
Author(s):  
Gerald Koelsch ◽  
Robert T. Turner ◽  
Lin Hong ◽  
Arun K. Ghosh ◽  
Jordan Tang

Mempasin 2, a ϐ-secretase, is the membrane-anchored aspartic protease that initiates the cleavage of amyloid precursor protein leading to the production of ϐ-amyloid and the onset of Alzheimer's disease. Thus memapsin 2 is a major therapeutic target for the development of inhibitor drugs for the disease. Many biochemical tools, such as the specificity and crystal structure, have been established and have led to the design of potent and relatively small transition-state inhibitors. Although developing a clinically viable mempasin 2 inhibitor remains challenging, progress to date renders hope that memapsin 2 inhibitors may ultimately be useful for therapeutic reduction of ϐ-amyloid.


1999 ◽  
Vol 97 (8) ◽  
pp. 967-976 ◽  
Author(s):  
M. Garay Salazar, J. M. Orea Rocha, A.

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