Protein Science, Vol 3, Issue 7 997-1009, Copyright © 1994 by Cold Spring Harbor Laboratory Press

ARTICLE

Side-chain entropy and packing in proteins

S. BROMBERG and K. A. DILL
Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143-1204

What role does side-chain packing play in protein stability and structure? To address this question, we compare a lattice model with side chains (SCM) to a linear lattice model without side chains (LCM). Self-avoiding configurations are enumerated in 2 and 3 dimensions exhaustively for short chains and by Monte Carlo sampling for chains up to 50 main-chain monomers long. This comparison shows that (1) side-chain degrees of freedom increase the entropy of open conformations, but side-chain steric exclusion decreases the entropy of compact conformations, thus producing a substantial entropy that opposes folding; (2) there is a side-chain ``freezing'' or ordering, i.e., a sharp decrease in entropy, near maximum compactness; and (3) the different types of contacts among side chains (s) and main-chain elements (m) have different frequencies, and the frequencies have different dependencies on compactness. mm contacts contribute significantly only at high densities, suggesting that mainchain hydrogen bonding in proteins may be promoted by compactness. The distributions of mm, ms, and ss contacts in compact SCM configurations are similar to the distributions in protein structures in the Brookhaven Protein Data Bank. We propose that packing in proteins is more like the packing of nuts and bolts in a jar than like the pairwise matching of jigsaw puzzle pieces.
CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. H. Hecht, A. Das, A. Go, L. H. Bradley, and Y. Wei De novo proteins from designed combinatorial libraries Protein Sci., July 1, 2004; 13(7): 1711 - 1723. [Abstract] [Full Text] [PDF]

				Y. Wei, T. Liu, S. L. Sazinsky, D. A. Moffet, I. Pelczer, and M. H. Hecht Stably folded de novo proteins from a designed combinatorial library Protein Sci., January 1, 2003; 12(1): 92 - 102. [Abstract] [Full Text] [PDF]

				R.I. Dima and D. Thirumalai Exploring protein aggregation and self-propagation using lattice models: Phase diagram and kinetics Protein Sci., May 1, 2002; 11(5): 1036 - 1049. [Abstract] [Full Text] [PDF]

				S. T. R. Walsh, H. Cheng, J. W. Bryson, H. Roder, and W. F. DeGrado Solution structure and dynamics of a de novo designed three-helix bundle protein PNAS, May 11, 1999; 96(10): 5486 - 5491. [Abstract] [Full Text] [PDF]

				J. R. Beasley and M. H. Hecht Protein Design: The Choice of de Novo Sequences J. Biol. Chem., January 24, 1997; 272(4): 2031 - 2034. [Full Text] [PDF]

				K. A. Dill and K. A. Dill Additivity Principles in Biochemistry J. Biol. Chem., January 10, 1997; 272(2): 701 - 704. [Full Text] [PDF]