Abstract

This research is directed toward developing greatly improved methods for sampling phase space in molecular systems having multiple conformations which are separated by significant energy barriers. The work will be important in converging free energy simulations of complex systems. The method we are exploring mixes stochastic dynamics (SD) and Metropolis Monte Carlo (MC) methods. The former method provides efficient local sampling while the MC facilitates transitions between the various conformational minima. We have shown that the mixed method is significantly more efficient than either method individually. Recently, we have developed an enhancement of the MC part of the algorithm in which directly jumping between conformational minima is allowed. This further increases the sampling efficiency by several orders of magnitude. In addition to algorithm development, we continue to develop potential functions and to compare our calculations with experiment.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
2P41RR006892-06
Application #
5225553
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1996
Total Cost
Indirect Cost

  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