Abstract

of protein dynamics is fundamental to an understanding of the relationship between structure and function for such diverse problems as: the binding of ligands to proteins, the catalytic activity of enzymes and the transport of ions through membranes. Computer simulations of protein dynamics constitute the most detailed theoretical approach available for studying the internal motions of proteins. The goals of this proposal are threefold: (1) to continue our major effort directed towards strengthening the connections between computer simulations and experimental probes of protein dynamics, (2) to explore the relationship between conformational flexibility and protein structure and function, and (3) to develop new and more accurate simulation techniques. The proteins currently being studied using simulation methods in our group include myoglobin, ovomucoid proteinase inhibitors and the complex of Rhizopus chinensis carboxyl proteinase with pepstatin. Additional model peptide systems are also being investigated.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM030580-07
Application #
3278362
Study Section
Biophysics and Biophysical Chemistry B Study Section (BBCB)
Project Start
1982-06-01
Project End
1990-05-31
Budget Start
1988-06-01
Budget End
1989-05-31
Support Year
7
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Rutgers University
Department
Type
Schools of Arts and Sciences
DUNS #
038633251
City
New Brunswick
State
NJ
Country
United States
Zip Code
08901

  Publications

Deng, Nanjie; Cui, Di; Zhang, Bin W et al. (2018) Comparing alchemical and physical pathway methods for computing the absolute binding free energy of charged ligands. Phys Chem Chem Phys 20:17081-17092
Haldane, Allan; Flynn, William F; He, Peng et al. (2018) Coevolutionary Landscape of Kinase Family Proteins: Sequence Probabilities and Functional Motifs. Biophys J 114:21-31
He, Peng; Zhang, Bin W; Arasteh, Shima et al. (2018) Conformational Free Energy Changes via an Alchemical Path without Reaction Coordinates. J Phys Chem Lett 9:4428-4435
Xia, Junchao; Flynn, William; Levy, Ronald M (2018) Improving Prediction Accuracy of Binding Free Energies and Poses of HIV Integrase Complexes Using the Binding Energy Distribution Analysis Method with Flattening Potentials. J Chem Inf Model 58:1356-1371
Cui, Di; Zhang, Bin W; Matubayasi, Nobuyuki et al. (2018) The Role of Interfacial Water in Protein-Ligand Binding: Insights from the Indirect Solvent Mediated Potential of Mean Force. J Chem Theory Comput 14:512-526
Zhang, Bin W; Cui, Di; Matubayasi, Nobuyuki et al. (2018) The Excess Chemical Potential of Water at the Interface with a Protein from End Point Simulations. J Phys Chem B 122:4700-4707
Harris, Robert C; Deng, Nanjie; Levy, Ronald M et al. (2017) Computing conformational free energy differences in explicit solvent: An efficient thermodynamic cycle using an auxiliary potential and a free energy functional constructed from the end points. J Comput Chem 38:1198-1208
Pal, Rajat Kumar; Haider, Kamran; Kaur, Divya et al. (2017) A combined treatment of hydration and dynamical effects for the modeling of host-guest binding thermodynamics: the SAMPL5 blinded challenge. J Comput Aided Mol Des 31:29-44
Levy, Ronald M; Cui, Di; Zhang, Bin W et al. (2017) Relationship between Solvation Thermodynamics from IST and DFT Perspectives. J Phys Chem B 121:3825-3841
Flynn, William F; Haldane, Allan; Torbett, Bruce E et al. (2017) Inference of Epistatic Effects Leading to Entrenchment and Drug Resistance in HIV-1 Protease. Mol Biol Evol 34:1291-1306

Showing the most recent 10 out of 105 publications