Abstract

Thisresearchisdirectedtowarddevelopinggreatlyimproved methods for sampling phase space in molecular systems having multiple conformations separated by significant energy barriers. The work will be important in obtaining converged free energies from simulations of complex chemical systems. Recently we developed a hybrid simulation system that mixes smart Monte Carlo and stochastic dynamics (MC(JBW)/SD). This method converges complex molecular systems quite rapidly because the Monte Carlo part of the algorithm is directed to preferently sample known low energy regions of conformational space (by Jumping Between Wells). In our MC(JBW)/SD simulation method, the MC(JBW) part of the algorithm operated only is a subset (e.g. torsions) of all available degrees of freedom. This past year we developed a pure MC(JBW) method that samples all degrees of freedom and generates the same ensembles as traditional Metropolis MonteCarlo - only much more rapidly. We have also used quantum mechanics to develop a new parameter set for carbohydrates and used it to compute conformational and anomeric free energies of simple sugars and oligosaccharides.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR006892-10
Application #
6314225
Study Section
Project Start
2000-05-05
Project End
2002-04-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
10
Fiscal Year
2000
Total Cost
$43,625
Indirect Cost

  Institution

Name
Columbia University (N.Y.)
Department
Type
DUNS #
049179401
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