help button home button Biophys. J.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bala, P.
Right arrow Articles by McCammon, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bala, P.
Right arrow Articles by McCammon, J. A.

Biophys J, September 2000, p. 1253-1262, Vol. 79, No. 3

Quantum-Dynamical Picture of a Multistep Enzymatic Process: Reaction Catalyzed by Phospholipase A2

P. Bała,*dagger P. Grochowski,* K. Nowinski,* B. Lesyng,*Dagger and J. A. McCammon§

 *Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University, 02-106 Warsaw, Poland;  dagger Institute of Physics, Nikolaus Copernicus University, 87-100 Torun, Poland;  Dagger Department of Biophysics, Warsaw University, 02-089 Warsaw, Poland; and  §Howard Hughes Medical Institute, and Department of Chemistry and Biochemistry and Department of Pharmacology, University of California at San Diego, La Jolla, California 92093-0365 USA

A quantum-classical molecular dynamics model (QCMD), applying explicit integration of the time-dependent Schrödinger equation (QD) and Newtonian equations of motion (MD), is presented. The model is capable of describing quantum dynamical processes in complex biomolecular systems. It has been applied in simulations of a multistep catalytic process carried out by phospholipase A2 in its active site. The process includes quantum-dynamical proton transfer from a water molecule to histidine localized in the active site, followed by a nucleophilic attack of the resulting OH- group on a carbonyl carbon atom of a phospholipid substrate, leading to cleavage of an adjacent ester bond. The process has been simulated using a parallel version of the QCMD code. The potential energy function for the active site is computed using an approximate valence bond (AVB) method. The dynamics of the key proton is described either by QD or classical MD. The coupling between the quantum proton and the classical atoms is accomplished via Hellmann-Feynman forces, as well as the time dependence of the potential energy function in the Schrödinger equation (QCMD/AVB model). Analysis of the simulation results with an Advanced Visualization System revealed a correlated rather than a stepwise picture of the enzymatic process. It is shown that an sp2right-arrow sp3 configurational change at the substrate carbonyl carbon is mostly responsible for triggering the activation process.

Biophys J, September 2000, p. 1253-1262, Vol. 79, No. 3
© 2000 by the Biophysical Society   0006-3495/00/09/1253/10  $2.00


This article has been cited by other articles:


Home page
 Protein Sci.Home page
J. Trylska, P. Grochowski, and J. A. McCammon
The role of hydrogen bonding in the enzymatic reaction catalyzed by HIV-1 protease
Protein Sci., February 1, 2004; 13(2): 513 - 528.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
J. Trylska, P. Bala, M. Geller, and P. Grochowski
Molecular Dynamics Simulations of the First Steps of the Reaction Catalyzed by HIV-1 Protease
Biophys. J., August 1, 2002; 83(2): 794 - 807.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. A. Lill and V. Helms
Proton shuttle in green fluorescent protein studied by dynamic simulations
PNAS, March 5, 2002; 99(5): 2778 - 2781.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2000 by the Biophysical Society.