Algorithms for Protein Folding

Felts, Tony

Abstract

This project is based upon the idea that, once secondary structure is specified, generation of the native protein conformation via computer simulation can be accomplished with relatively simple potential functions and algorithms. We have successfully folded several proteins (myoglobin, 1-CTF, myohemerythrin, cytochrome b-256) to a resolution of ~ 4-6 A RMS using this strategy, and our code has been implemented on both IBM workstations and the CM-5 where efficient parallelization has been achieved. We are currently working on improving the potential functions to deal with difficult cases (R69) and developing specialized algorithms for treating twisted B-strands (which were not allowed in the original algorithm). We are also investigating a new minimization algorithm, based upon the branch and bound procedure of Floudas.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Center for Research Resources (NCRR)
• Type: Biotechnology Resource Grants (P41)
• Project #: 2P41RR006892-06
• Application #: 5225539
• Support Year: 6
• Fiscal Year: 1996

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