. This research is intended to increase our understanding of diffusion-controlled processes in biology. More precisely, theoretical and computational work will be done to provide increasingly detailed and accurate analyses of the rates of diffusion-controlled enzymatic reactions. A few selected biomolecular systems will be studied in great depth. This approach should facilitate the discovery of concepts of broad relevance in addition to clarifying the mechanisms of the particular systems chosen for study. Comparisons will be made to experimental data obtained under a variety of conditions, both to test the theoretical models and to aid in the interpretation of the experiments. Other parts of the proposed work involve the development of tools for diffusional simulations and, secondarily, for the calculation of electrostatic forces, which are of special importance in influencing biomolecular diffusion. Among the specific questions that this project will seek to answer are the following. How do the effects of modifications at different sites combine to produce changes in the catalytic rate of Cu, Zn superoxide dismutase (SOD)? How can simulations of the diffusional encounter of substrate with the surface of SOD be combined with detailed simulations of subsequent events to provide a more complete description of SOD activity? Can the tools developed in this work be extended to enzymes such as Mn SOD and triose phosphate isomerase (TIM), where successively larger motions in the enzyme may modulate substrate access to the active site? The health relatedness of this work is in the tools it should yield for the rational design of molecules with desired kinetic properties. E.G., SOD is being considered for pharmacologic use; the methods developed in this work could help in engineering SOD to increase its diffusion-controlled rate of action.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM031749-09
Application #
3280025
Study Section
Special Emphasis Panel (SSS (A))
Project Start
1983-06-01
Project End
1995-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
9
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Houston
Department
Type
Schools of Arts and Sciences
DUNS #
800771594
City
Houston
State
TX
Country
United States
Zip Code
77204
Guan, W; Cheng, X; Huang, J et al. (2018) RPYFMM: Parallel Adaptive Fast Multipole Method for Rotne-Prager-Yamakawa Tensor in Biomolecular Hydrodynamics Simulations. Comput Phys Commun 227:99-108
Jurrus, Elizabeth; Engel, Dave; Star, Keith et al. (2018) Improvements to the APBS biomolecular solvation software suite. Protein Sci 27:112-128
Huang, Yu-Ming M; Huber, Gary A; Wang, Nuo et al. (2018) Brownian dynamic study of an enzyme metabolon in the TCA cycle: Substrate kinetics and channeling. Protein Sci 27:463-471
Caliman, Alisha D; Miao, Yinglong; McCammon, James A (2018) Mapping the allosteric sites of the A2A adenosine receptor. Chem Biol Drug Des 91:5-16
Utesch, Tillmann; de Miguel Catalina, Alejandra; Schattenberg, Caspar et al. (2018) A Computational Modeling Approach Predicts Interaction of the Antifungal Protein AFP from Aspergillus giganteus with Fungal Membranes via Its ?-Core Motif. mSphere 3:
Zhang, Jingbo; Wang, Nuo; Miao, Yinglong et al. (2018) Identification of SLAC1 anion channel residues required for CO2/bicarbonate sensing and regulation of stomatal movements. Proc Natl Acad Sci U S A 115:11129-11137
Miao, Yinglong; McCammon, J Andrew (2018) Mechanism of the G-protein mimetic nanobody binding to a muscarinic G-protein-coupled receptor. Proc Natl Acad Sci U S A 115:3036-3041
Palermo, Giulia; Chen, Janice S; Ricci, Clarisse G et al. (2018) Key role of the REC lobe during CRISPR-Cas9 activation by 'sensing', 'regulating', and 'locking' the catalytic HNH domain. Q Rev Biophys 51:
Ricci, Clarisse G; Li, Bo; Cheng, Li-Tien et al. (2017) ""Martinizing"" the Variational Implicit Solvent Method (VISM): Solvation Free Energy for Coarse-Grained Proteins. J Phys Chem B 121:6538-6548
Dick, Benjamin L; Patel, Ashay; McCammon, J Andrew et al. (2017) Effect of donor atom identity on metal-binding pharmacophore coordination. J Biol Inorg Chem 22:605-613

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