Spatial profiling of protein hydrophobicity: Native vs. Decoy structures

• Published in: Proteins, structure, function, and bioinformatics Vol. 52; no. 4; pp. 561 - 572
• Main Authors: Zhou, Ruhong, Silverman, B. David, Royyuru, Ajay K., Athma, Prasanna
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.09.2003
• Subjects: Algorithms; Amino Acids - chemistry; Databases, Protein; globular proteins; Hydrophobic and Hydrophilic Interactions; hydrophobic profiling; hydrophobic ratio; hydrophobic score; Protein Conformation; protein decoys; Protein Folding; Protein Structure, Secondary; Proteins - chemistry; second-order moment; Thermodynamics
• ISSN: 0887-3585; 1097-0134
• DOI: 10.1002/prot.10419

A recent study of 30 soluble globular protein structures revealed a quasi‐invariant called the hydrophobic ratio. This invariant, which is the ratio of the distance at which the second order hydrophobic moment vanished to the distance at which the zero order moment vanished, was found to be 0.75 ± 0.05 for 30 protein structures. This report first describes the results of the hydrophobic profiling of 5,387 non‐redundant globular protein domains of the Protein Data Bank, which yields a hydrophobic ratio of 0.71 ± 0.08. Then, a new hydrophobic score is defined based on the hydrophobic profiling to discriminate native‐like proteins from decoy structures. This is tested on three widely used decoy sets, namely the Holm and Sander decoys, Park and Levitt decoys, and Baker decoys. Since the hydrophobic moment profiling characterizes a global feature and requires reasonably good statistics, this imposes a constraint upon the size of the protein structures in order to yield relatively smooth moment profiles. We show that even subject to the limitations of protein size (both Park & Levitt and Baker sets are small protein decoys), the hydrophobic moment profiling and hydrophobic score can provide useful information that should be complementary to the information provided by force field calculations. Proteins 2003;52:561–572. © 2003 Wiley‐Liss, Inc.