Journal
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
Volume 60, Issue 1, Pages 46-65Publisher
WILEY
DOI: 10.1002/prot.20438
Keywords
higher order interactions; many-body interactions; 3-body potential; nonadditive effects; nonadditive coefficient; cooperativity; anticooperativity
Categories
Funding
- NIGMS NIH HHS [GM68958] Funding Source: Medline
Ask authors/readers for more resources
Characterizing multibody interactions of hydrophobic, polar, and ionizable residues in protein is important for understanding the stability of protein structures. We introduce a geometric model for quantifying 3-body interactions in native proteins. With this model, empirical propensity values for many types of 3-body interactions can be reliably estimated from a database of native protein structures, despite the overwhelming presence of pairwise contacts. In addition, we define a nonadditive coefficient that characterizes cooperativity and anticooperativity of residue interactions in native proteins by measuring the deviation of 3-body interactions from 3 independent pairwise interactions. It compares the 3-body propensity value from what would be expected if only pairwise interactions were considered, and highlights the distinction of propensity and cooperativity of 3-body interaction. Based on the geometric model, and what can be inferred from statistical analysis of such a model, we find that hydrophobic interactions and hydrogen-bonding interactions make nonadditive contributions to protein stability, but the nonadditive nature depends on whether such interactions are located in the protein interior or on the protein surface. When located in the interior, many hydrophobic interactions such as those involving alkyl residues are anticooperative. Salt-bridge and regular hydrogen-bonding interactions, such as those involving ionizable residues and polar residues, are cooperative. When located on the protein surface, these salt-bridge and regular hydrogen-bonding interactions are anticooperative, and hydrophobic interactions involving alkyl residues become cooperative. We show with examples that incorporating 3-body interactions improves discrimination of protein native structures against decoy conformations. In addition, analysis of cooperative 3-body interaction may reveal spatial motifs that can suggest specific protein functions. (c) 2005 Wiley-Liss, Inc.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available