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Side‐chain entropy and packing in proteins
Author(s) -
Bromberg Sarina,
Dill Ken A.
Publication year - 1994
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560030702
Subject(s) - side chain , crystallography , compact space , entropy (arrow of time) , steric effects , conformational entropy , chemical physics , lattice (music) , hydrogen bond , chemistry , physics , statistical physics , mathematics , thermodynamics , stereochemistry , polymer , molecule , pure mathematics , quantum mechanics , nuclear magnetic resonance , acoustics
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 main‐chain 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.