Abstract

The goal of this research is the development of more accurate methods for molecular simulations of solvated proteins, and their application to forefront problems in structural biology and biophysical chemistry. There are three specific aims: (1) further develop implicit solvent all atom effective potentials for biomolecular simulations and methods for their optimization, (2) use these implicit solvent models to: explore the molecular basis for protein-ligand binding specificity, study the native to molten globule protein """"""""melting"""""""" transition, continue work on protein structure determination using sparse experimental data, and (3) characterize protein dynamics more accurately and over longer times, by combining information from simulations with those from NMR and single molecule optical experiments analyzed in new ways. These projects will build on the progress made during the current grant period in the development of """"""""state of the art"""""""" effective potentials for protein simulations and forefront applications which are best suited to investigation using all atom models.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM030580-23
Application #
6773869
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Program Officer
Wehrle, Janna P
Project Start
1982-06-01
Project End
2007-07-31
Budget Start
2004-08-01
Budget End
2005-07-31
Support Year
23
Fiscal Year
2004
Total Cost
$309,342
Indirect Cost

  Institution

Name
Rutgers University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
001912864
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
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
Zhang, Bin W; Deng, Nanjie; Tan, Zhiqiang et al. (2017) Stratified UWHAM and Its Stochastic Approximation for Multicanonical Simulations Which Are Far from Equilibrium. J Chem Theory Comput 13:4660-4674

Showing the most recent 10 out of 105 publications