Computational Grand Challenge Applications Projects

Complex Enzymatic Reactions

Volkhard Helms (1), T. P. Straatsma (2), Thereza A. Soares Da Silva (2), Hartmut Michel (3), Markus Elstner (4)

(1)Saarland University, Germany, (2)Pacific Northwest National Laboratory, (3)Max Planck Institute of Biophysics, Germany, (4)Technical University Braunschweig, Germany


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.