Abstract

The development of a set of transferable intermolecular potential functions (TIPS) describing water-protein interactions is proposed. This represents an extension of the TIPS for water, alkanes, alcohols, and ethers that have already been demonstrated to yield good thermodynamic and structural results for pure liquids and dilute solutions in statistical mechanics simulations. The TIPS parameters for biochemical systems will be chosen to reproduce experimental data for pure liquid amides, for aqueous solutions of amides and for various organic systems representing side chains. Comparisons will also be made with high quality ab initio quantum mechanical calculations for hydrogen bonded complexes. The proposed work will entail numerous Monte Carlo simulations of pure liquids and aqueous solutions that will yield detailed insights into the hydration of protein constituents, the nature of hydrophobic effects and the structure of liquid amides. The availability of TIPS for biochemical systems will be of great utility to biophysicists interested in studying problems such as the hydration of macromolecules including the location of localized water molecules in protein crystals and in active sites of enzymes, enzyme-substrate binding, the conformations of polypeptides and their denaturation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM032136-03
Application #
3280762
Study Section
Biophysics and Biophysical Chemistry A Study Section (BBCA)
Project Start
1983-07-01
Project End
1986-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Purdue University
Department
Type
Schools of Arts and Sciences
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907

  Publications

Trivedi-Parmar, Vinay; Robertson, Michael J; Cisneros, José A et al. (2018) Optimization of Pyrazoles as Phenol Surrogates to Yield Potent Inhibitors of Macrophage Migration Inhibitory Factor. ChemMedChem 13:1092-1097
Cabeza de Vaca, Israel; Qian, Yue; Vilseck, Jonah Z et al. (2018) Enhanced Monte Carlo Methods for Modeling Proteins Including Computation of Absolute Free Energies of Binding. J Chem Theory Comput 14:3279-3288
Dodda, Leela S; Tirado-Rives, Julian; Jorgensen, William L (2018) Unbinding Dynamics of Non-Nucleoside Inhibitors from HIV-1 Reverse Transcriptase. J Phys Chem B :
Trivedi-Parmar, Vinay; Jorgensen, William L (2018) Advances and Insights for Small Molecule Inhibition of Macrophage Migration Inhibitory Factor. J Med Chem 61:8104-8119
Dawson, Thomas K; Dziedzic, Pawel; Robertson, Michael J et al. (2017) Adding a Hydrogen Bond May Not Help: Naphthyridinone vs Quinoline Inhibitors of Macrophage Migration Inhibitory Factor. ACS Med Chem Lett 8:1287-1291
Chan, Albert H; Lee, Won-Gil; Spasov, Krasimir A et al. (2017) Covalent inhibitors for eradication of drug-resistant HIV-1 reverse transcriptase: From design to protein crystallography. Proc Natl Acad Sci U S A 114:9725-9730
Dodda, Leela S; Vilseck, Jonah Z; Tirado-Rives, Julian et al. (2017) 1.14*CM1A-LBCC: Localized Bond-Charge Corrected CM1A Charges for Condensed-Phase Simulations. J Phys Chem B 121:3864-3870
Robertson, Michael J; Tirado-Rives, Julian; Jorgensen, William L (2017) Improved Treatment of Nucleosides and Nucleotides in the OPLS-AA Force Field. Chem Phys Lett 683:276-280
Yan, Xin Cindy; Robertson, Michael J; Tirado-Rives, Julian et al. (2017) Improved Description of Sulfur Charge Anisotropy in OPLS Force Fields: Model Development and Parameterization. J Phys Chem B 121:6626-6636
Dodda, Leela S; Cabeza de Vaca, Israel; Tirado-Rives, Julian et al. (2017) LigParGen web server: an automatic OPLS-AA parameter generator for organic ligands. Nucleic Acids Res 45:W331-W336

Showing the most recent 10 out of 117 publications