An Ab Initio QM/MM Study of the Electrostatic Contribution to Catalysis in the Active Site of Ketosteroid Isomerase

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Xianwei Wang, Xiao He

Abstract

The electric field in the hydrogen-bond network of the active site of ketosteroid isomerase (KSI) has been experimentally measured using vibrational Stark effect (VSE) spectroscopy, and utilized to study the electrostatic contribution to catalysis. A large gap was found in the electric field between the computational simulation based on the Amber force field and the experimental measurement. In this work, quantum mechanical (QM) calculations of the electric field were performed using an ab initio QM/MM molecular dynamics (MD) simulation and electrostatically embedded generalized molecular fractionation with conjugate caps (EE-GMFCC) method. Our results demonstrate that the QM-derived electric field based on the snapshots from QM/MM MD simulation could give quantitative agreement with the experiment. The accurate calculation of the electric field inside the protein requires both the rigorous sampling of configurations, and a QM description of the electrostatic field. Based on the direct QM calculation of the electric field, we theoretically confirmed that there is a linear correlation relationship between the activation free energy and the electric field in the active site of wild-type KSI and its mutants (namely, D103N, Y16S, a...Continue Reading

References

Jan 6, 1995·Science·A Radzicka, R Wolfenden
Aug 31, 2000·Annual Review of Biochemistry·D Hilvert
Apr 30, 2004·Journal of Computational Chemistry·Junmei WangDavid A Case
Jan 6, 2005·Journal of the American Chemical Society·Karin NienhausG Ulrich Nienhaus
Mar 3, 2005·The Journal of Chemical Physics·Xiao He, John Z H Zhang
Oct 4, 2005·Journal of Computational Chemistry·David A CaseRobert J Woods
Feb 7, 2006·Journal of Molecular Graphics & Modelling·Junmei WangDavid A Case
Aug 10, 2006·Chemical Reviews·Arieh WarshelMats H M Olsson
Mar 1, 2012·The Journal of Physical Chemistry. B·Li L DuanJohn Z H Zhang
Mar 23, 2013·The Journal of Physical Chemistry. a·Xianwei WangJohn Z H Zhang
Apr 10, 2014·Journal of Molecular Modeling·Li L DuanJohn Z H Zhang
May 24, 2014·Accounts of Chemical Research·Xiao HeJohn Z H Zhang
Jun 3, 2014·Accounts of Chemical Research·Changge Ji, Ye Mei
Dec 2, 2014·Dalton Transactions : an International Journal of Inorganic Chemistry·Camille LatoucheVincenzo Barone
Mar 24, 2015·Accounts of Chemical Research·Stephen D Fried, Steven G Boxer
Apr 7, 2015·Chemical Reviews·Michael A Collins, Ryan P A Bettens
Aug 14, 2012·Journal of Chemical Theory and Computation·Daniel J SandbergJosé A Gascón
Dec 9, 2015·Journal of Chemical Theory and Computation·Jinfeng LiuJohn Z H Zhang
Dec 22, 2015·Physical Chemistry Chemical Physics : PCCP·Jinfeng LiuXiao He
Mar 5, 2016·Nature·Albert C AragonèsMichelle L Coote
Aug 23, 2016·Journal of the American Chemical Society·Yufan Wu, Steven G Boxer
May 1, 2018·Journal of Computational Chemistry·Yaqian WangXiao He

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Citations

Apr 10, 2021·The Journal of Chemical Physics·Xianwei WangJohn Z H Zhang
Aug 2, 2019·Journal of the American Chemical Society·Valerie Vaissier Welborn, Teresa Head-Gordon
Sep 16, 2021·Physical Chemistry Chemical Physics : PCCP·Xianwei WangJohn Z H Zhang

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Methods Mentioned

BETA
X-ray

Software Mentioned

Gaussian
EE
Gaussian09
CHARMM
ANTECHAMBER
PyMOL
AMBER12
GMFCC
AMBER

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