Complex Enzymatic Reactions
EMSL Project ID
20896
Abstract
This proposal seeks computational resources for the continued development and application of modeling capabilities for the study of complex enzymatic reactions, in particular those that involve proton transfer steps, and novel free energy methodologies for enzymatic design. Understanding of the molecular-level processes, including proton transfer steps in long-time conformational protein dynamical processes as well as the rational design of enzymes with improved specificity requires extending computational tools and techniques beyond what is currently available. The primary approach is that of new developments in the QHOP and DFTB methodologies which will be implemented as new capabilities of NWChem. The second approach deals with a novel application of free-energy perturbation techniques. Both approaches will involve design and implementation of a meta-simulation engine that controls the launch and analysis of individual MD trajectories.
Project Details
Project type
Capability Research
Start Date
2006-10-31
End Date
2009-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Gomes DE, RD Lins, PG Pascutti, TP Straatsma, and TA Soares. 2008. "Molecular Models to Emulate Confinement Effects on the Internal Dynamics of Organophosphorous Hydrolase." In Lecture Notes in Computer Science: Advances in Bioinformatics and Computational Biology, Third Brazilian Symposium on Bioinformatics, BSB 2008, Santo André, Brazil, August 28-30, 2008. Proceedings, vol. 5167, ed. S. Istrail, P. Pevzner, and M.Waterman, pp. 68-78. Springer, New York, NY. doi:10.1007/978-3-540-85557-6_7
Gu W, and VH Helms. 2007. "Different Protonation Equilibria of 4-Methylimidazole and Acetic Acid." Chemphyschem 8(17):2445-2451. doi:10.1002/cphc.200700442
Lei C, TA Soares, Y Shin, J Liu, and EJ Ackerman. 2008. "Enzyme Specific Activity in Functionalized Nanoporous Supports." Nanotechnology 19(12):Art. No. 125102. doi:10.1088/0957-4484/19/12/125102
Soares TA, MA Osman, and T Straatsma. 2007. "Molecular Dynamics of Organophosphorous Hydrolases Bound to the Nerve Agent Soman." Journal of Chemical Theory and Computation 3(4):1569-1579.