Abstract

Wehavedevelopedanalgorithmforcarryingoutquantumchemical calculations in a dielectric medium. Our electronic structure program PSGVB first calculates electrostatic point charges using an ESP fitting method. These charges are then passed to DELPHI which determines the reaction filed by solving the Poisson-Boltzmann equation. The reaction field is represented as point charges on the dielectric boundary. These are passed to PSGVB which now solves quantum chemical equations in the field of the point charges. This process is iterated until self-consistency is reached. We have shown that if one uses accurate gas phase quantum chemical methods (GVB plus a good basis set is sufficient) solvation energies accurate to ~0.6kcal/mole can be computed for a test set of 29 molecules. Recent work includes development of an analytical gradient method using a novel finite element Poisson-Boltzmann solver and improvement of the accuracy of the continuum method via inclusion of corrections for short-range hydrogen bonding terms.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR006892-09
Application #
6122703
Study Section
Project Start
1999-05-05
Project End
2000-05-04
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
9
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

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

  Publications

Halgren, Thomas A; Murphy, Robert B; Friesner, Richard A et al. (2004) Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. J Med Chem 47:1750-9
Friesner, Richard A; Banks, Jay L; Murphy, Robert B et al. (2004) Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem 47:1739-49
Baik, Mu-Hyun; Friesner, Richard A; Lippard, Stephen J (2003) Theoretical study of cisplatin binding to purine bases: why does cisplatin prefer guanine over adenine? J Am Chem Soc 125:14082-92
Baik, Mu-Hyun; Friesner, Richard A; Lippard, Stephen J (2002) Theoretical study on the stability of N-glycosyl bonds: why does N7-platination not promote depurination? J Am Chem Soc 124:4495-503
An, Yuling; Friesner, Richard A (2002) A novel fold recognition method using composite predicted secondary structures. Proteins 48:352-66
Gallicchio, Emilio; Zhang, Linda Yu; Levy, Ronald M (2002) The SGB/NP hydration free energy model based on the surface generalized born solvent reaction field and novel nonpolar hydration free energy estimators. J Comput Chem 23:517-29
Friesner, R A; Dunietz, B D (2001) Large-scale ab initio quantum chemical calculations on biological systems. Acc Chem Res 34:351-8
Gherman, B F; Dunietz, B D; Whittington, D A et al. (2001) Activation of the C-H bond of methane by intermediate Q of methane monooxygenase: a theoretical study. J Am Chem Soc 123:3836-7
Standley, D M; Eyrich, V A; An, Y et al. (2001) Protein structure prediction using a combination of sequence-based alignment, constrained energy minimization, and structural alignment. Proteins Suppl 5:133-9
Eyrich, V A; Standley, D M; Friesner, R A (1999) Prediction of protein tertiary structure to low resolution: performance for a large and structurally diverse test set. J Mol Biol 288:725-42

Showing the most recent 10 out of 22 publications