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Geometric cooperativity and anticooperativity of three‐body interactions in native proteins
Author(s) -
Li Xiang,
Liang Jie
Publication year - 2005
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.20438
Subject(s) - cooperativity , salt bridge , hydrophobic effect , hydrogen bond , chemistry , lattice protein , non covalent interactions , pairwise comparison , protein–protein interaction , chemical physics , protein structure , biological system , computational chemistry , crystallography , molecule , mathematics , biochemistry , biology , statistics , organic chemistry , mutant , gene
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. Proteins 2005. © 2005 Wiley‐Liss, Inc.