Bulletin of the American Physical Society
2007 APS March Meeting
Volume 52, Number 1
Monday–Friday, March 5–9, 2007; Denver, Colorado
Session S5: Quantum Mechanics/Molecular Mechanics: Developments and Applications |
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Sponsoring Units: DBP Chair: Victor Batista, Yale University Room: Colorado Convention Center Korbel 1A-1B |
Wednesday, March 7, 2007 2:30PM - 3:06PM |
S5.00001: Modeling Enzymatic Reactions in Proteins. Invited Speaker: We will discuss application of our density functional (DFT)-based QM/MM methodology to modeling a variety of protein active sites, including methane monooxygenase, myoglobin, and cytochrome P450.~ In addition to the calculation of intermediates, transition states, and rate constants, we will discuss modeling of reactions requiring protein conformational changes. Our methodology reliably achieves small errors as a result of imposition of the QM/MM boundary.~ However, the accuracy of DFT methods can vary significantly with the type of system under study. We will discuss a novel approach to the reduction of errors in gradient corrected and hybrid DFT functionals, using empirical localized orbital corrections (DFT-LOC), which addresses this problem effectively.~ For example, the mean unsigned error in atomization energies for the G3 data set using the B3LYP-LOC model is 0.8 kcal/mole, as compared with 4.8 kcal/mole for B3LYP and 1.0 kcal/mole for G3 theory. [Preview Abstract] |
Wednesday, March 7, 2007 3:06PM - 3:42PM |
S5.00002: Challenges and advances in QM/MM methods for studies of energetics and dynamics of biological systems Invited Speaker: QM/MM approaches have become a popular tool in studies of large systems, yet the use of such approaches in accurate evaluations of reaction rates in proteins and solutions is very challenging. Unfortunately, quantitative studies require a combination of accurate (ab intitio based) potential surfaces and the ability of extensive sampling for proper evaluation of activation free energies and transmission factors. Our strategies for overcoming these problems are based on the use of an EVB potential surface as reference potential for ab initio sampling. The use of this powerful approach for studies of the redox potential of blue copper proteins and related problems, the autoionization of water in water and some enzymatic reactions will be described, emphasizing the requirements of stable and reliable results for biological processes. [Preview Abstract] |
Wednesday, March 7, 2007 3:42PM - 4:18PM |
S5.00003: QM/MM in complex systems using SCC-DFTB and its implementation in Amber. Invited Speaker: We will present our current implementation of SCC-DFTB into the molecular dynamics program Amber. Details of the efficiency and accuracy of the method will be presented. We will also shows some case studies involving conformational searches in peptides, replica exchange simulations in solution, and an application to an enzyme mechanism. [Preview Abstract] |
Wednesday, March 7, 2007 4:18PM - 4:54PM |
S5.00004: Improved QM Methods and Their Application in QM/MM Studies of Enzymatic Reactions Invited Speaker: Quantum mechanics (QM) and Monte Carlo statistical mechanics (MC) simulations have been used by us since the early 1980s to study reaction mechanisms and the origin of solvent effects on reaction rates. A goal was always to perform the QM and MC/MM calculations simultaneously in order to obtain free-energy surfaces in solution with no geometrical restrictions. This was achieved by 2002 and complete free-energy profiles and surfaces with full sampling of solute and solvent coordinates can now be obtained through one job submission using BOSS [JCC 2005, 26, 1689]. Speed and accuracy demands also led to development of the improved semiempirical QM method, PDDG-PM3 [JCC 1601 (2002); JCTC 817 (2005)]. The combined PDDG-PM3/MC/FEP methodology has provided excellent results for free energies of activation for many reactions in numerous solvents. Recent examples include Cope, Kemp and E1cb eliminations [JACS 8829 (2005), 6141 (2006); JOC 4896 (2006)], as well as enzymatic reactions catalyzed by the putative Diels-Alderase, macrophomate synthase, and fatty-acid amide hydrolase [JACS 3577 (2005); JACS (2006)]. The presentation will focus on the accuracy that is currently achievable in such QM/MM studies and the accuracy of the underlying QM methodology including extensive comparisons of results from PDDG-PM3 and ab initio DFT methods. [Preview Abstract] |
Wednesday, March 7, 2007 4:54PM - 5:30PM |
S5.00005: Local and global refinement of electronic and structural properties of proteins via QM/MM Invited Speaker: This talk presents a new method to incorporate polarization effects in the electrostatic potential of proteins and enzymes, with potential application to even larger biological systems such as ribosomes. Polarization effects are incorporated via an iterative self-consistent point-charge model of the protein electrostatic potential. The method, which scales linearly with the size of the protein, achieves quantitative agreement with full QM calculations in the description of electrostatic potentials of small polypeptides where polarization effects are significant, showing a remarkable improvement relative to the corresponding electrostatic potentials obtained with popular MM force fields. The capabilities of the method will be demonstrated in several applications, including calculations of the electrostatic potential in the potassium channel protein and the description of protein-protein association. [Preview Abstract] |
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