Abstract

This proposal describes development of computational methods and software to study metalloprotein active sites, and applications to a number of specific proteins. The methods include correlated ab initio quantum chemistry with large basis sets, continuum solvation models based on a self-consistent reaction field formalism, and mixed quantum mechamcal/molecular techniques. New algorithmic approaches, with demonstrated improvements in computational efficiency and accuracy, are described in each of these areas. Applications include studies of electron transfer in the photosynthetic reaction center, catlyatic mechanisms of the enzymes methane monooxygenase and ribonucleotide reductase, and redox potentials of iron sulfur proteins.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM040526-14
Application #
6385740
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Program Officer
Flicker, Paula F
Project Start
1988-07-01
Project End
2003-06-30
Budget Start
2001-07-01
Budget End
2002-06-30
Support Year
14
Fiscal Year
2001
Total Cost
$173,310
Indirect Cost

  Institution

Name
Columbia University (N.Y.)
Department
Chemistry
Type
Other Domestic Higher Education
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027

  Publications

Friesner, Richard A; Abel, Robert; Goldfeld, Dahlia A et al. (2013) Computational methods for high resolution prediction and refinement of protein structures. Curr Opin Struct Biol 23:177-84
Zeiske, Tim; Stafford, Kate A; Friesner, Richard A et al. (2013) Starting-structure dependence of nanosecond timescale intersubstate transitions and reproducibility of MD-derived order parameters. Proteins 81:499-509
Miller, Edward B; Murrett, Colleen S; Zhu, Kai et al. (2013) Prediction of Long Loops with Embedded Secondary Structure using the Protein Local Optimization Program. J Chem Theory Comput 9:1846-4864
Li, Jianing; Abel, Robert; Zhu, Kai et al. (2011) The VSGB 2.0 model: a next generation energy model for high resolution protein structure modeling. Proteins 79:2794-812
Li, Jianing; Schneebeli, Severin T; Bylund, Joseph et al. (2011) IDSite: An accurate approach to predict P450-mediated drug metabolism. J Chem Theory Comput 7:3829-3845
Bochevarov, Arteum D; Li, Jianing; Song, Woon Ju et al. (2011) Insights into the different dioxygen activation pathways of methane and toluene monooxygenase hydroxylases. J Am Chem Soc 133:7384-97
Wang, Lingle; Friesner, Richard A; Berne, B J (2011) Replica exchange with solute scaling: a more efficient version of replica exchange with solute tempering (REST2). J Phys Chem B 115:9431-8
Bochevarov, Arteum D; Friesner, Richard A; Lippard, Stephen J (2010) The prediction of Fe Mössbauer parameters by the density functional theory: a benchmark study. J Chem Theory Comput 6:3735-3749
Schneebeli, Severin T; Hall, Michelle Lynn; Breslow, Ronald et al. (2009) Quantitative DFT modeling of the enantiomeric excess for dioxirane-catalyzed epoxidations. J Am Chem Soc 131:3965-73
Tian, Li; Friesner, Richard A (2009) QM/MM Simulation on P450 BM3 Enzyme Catalysis Mechanism. J Chem Theory Comput 5:1421-1431

Showing the most recent 10 out of 45 publications