Modeling Side Chains in Peptides and Proteins with the Locally Enhanced Sampling/Simulated Annealing Method
In this chapter, we present the formal basis of a new optimization method that we call LES (locally enhanced sampling) together with applications to side-chain modeling in peptides and proteins. We examine the relationship between an energy function that is derived from data on small model systems and the correct structure of the protein. The question is: Given a functional form for the potential energy of a macromolecule, are the side-chain coordinates at the global energy minimum similar to the x-ray coordinates? This comparison enables us to detect inaccuracies in the force fields that we used (Brooks et al., 1983; Jorgensen and Tirado-Rives, 1988) and possibly to improve them.
KeywordsForce Field Potential Energy Surface Freezing Temperature Residue Type Minimum Energy Path
Unable to display preview. Download preview PDF.
- Elber R, Roitberg A, Simmering C, Goldstein R, Verkhiver G, Li H, Ulitsky A (1993): MOIL: A molecular dynamics program with emphasis in conformational searches and reaction path calculations. To be published in the proceedings of the NATO conference: Statistical Mechanics, Protein Structure and Protein-Substrate Interactions, Doniac S, ed., New York: Plenum Press. This program is available via anonymous ftp from 126.96.36.199Google Scholar
- Roitberg A (1992): Ph.D. thesis, University of Illinois at ChicagoGoogle Scholar
- Shalloway D (1992): In Recent Advances in Global Optimization, Floudas A, Pardalos PM, eds. Princeton, NJ: Princeton University Press, pp. 433–477Google Scholar
- Tuffery P, Etchebest C, Hazout S, Lavery R (1991): A new approach to the rapid determination of protein side-chain conformations. J Biomo/Struc Dynamics 8:1267–1289Google Scholar