DOI: 10.1002/pro.5560060106. Studies of protein‐protein interfaces: A statistical analysis of the hydrophobic effect

Studies of protein‐protein interfaces: A statistical analysis of the hydrophobic effect

10.1002/pro.5560060106

Crossref journal-article

Wiley

Protein Science (311)

Abstract

AbstractData sets of 362 structurally nonredundant protein‐protein interfaces and of 57 symmetry‐related oligomeric interfaces have been used to explore whether the hydrophobic effect that guides protein folding is also the main driving force for protein‐protein associations. The buried nonpolar surface area has been used to measure the hydrophobic effect. Our analysis indicates that, although the hydrophobic effect plays a dominant role in protein‐protein binding, it is not as strong as that observed in the interior of protein monomers. Comparison of the interiors of the monomers with those of the interfaces reveals that, in general, the hydrophobic amino acids are more frequent in the interior of the monomers than in the interior of the protein‐protein interfaces. On the other hand, a higher proportion of charged and polar residues are buried at the interfaces, suggesting that hydrogen bonds and ion pairs contribute more to the stability of protein binding than to that of protein folding. Moreover, comparison of the interior of the interfaces to protein surfaces indicates that the interfaces are poorer in polar/charged than the surfaces and are richer in hydrophobic residues. The interior of the interfaces appears to constitute a compromise between the stabilization contributed by the hydrophobic effect on the one hand and avoiding patches on the protein surfaces that are too hydrophobic on the other. Such patches would be unfavorable for the unassociated monomers in solution. We conclude that, although the types of interactions are similar between protein‐protein interfaces and single‐chain proteins overall, the contribution of the hydrophobic effect to protein‐protein associations is not as strong as to protein folding. This implies that packing patterns and interatom, or interresidue, pairwise potential functions, derived from monomers, are not ideally suited to predicting and assessing ligand associations or design. These would perform adequately only in cases where the hydrophobic effect at the binding site is substantial.

Bibliography

Tsai, C., Lin, S. L., Wolfson, H. J., & Nussinov, R. (1997). Studies of proteinâprotein interfaces: A statistical analysis of the hydrophobic effect. Protein Science, 6(1), 53â64. Portico.

Authors 4

Chung‐Jung Tsai (first)
Shuo Liang Lin (additional)
Haim J. Wolfson (additional)
Ruth Nussinov (additional)

References 24 Referenced 343

10.1002/pro.5560030601
10.1016/S0022-2836(77)80200-3
10.1002/jcc.540040211
10.1038/357543a0
10.1002/prot.340210406
10.1016/0022-2836(87)90189-6
10.1006/jmbi.1995.0481
{'key': 'e_1_2_1_9_1', 'first-page': '7134', 'article-title': 'Dominant forces in protein folding', 'volume': '31', 'author': 'Dill KA', 'year': '1990', 'journal-title': 'Biochemistry'} / Biochemistry / Dominant forces in protein folding by Dill KA (1990)
10.1016/0079-6107(87)90013-7
10.1002/prot.340230413
10.1073/pnas.93.1.13
10.1002/prot.340090106
10.1016/0022-2836(71)90324-X
10.1006/jmbi.1995.0208
10.1016/0022-2836(87)90038-6
10.1002/pro.5560031202
10.1093/oso/9780199633968.003.0007 / Mechanisms of protein folding by Price NC (1994)
10.1016/0076-6879(94)28025-8
10.1016/0022-2836(73)90011-9
10.1006/jmbi.1996.0424
10.3109/10409239609106582
10.1002/prot.340200405
10.1016/0022-2836(92)90506-F
10.1002/pro.5560030501

Dates

Type	When
Created	15 years, 1 month ago (July 12, 2010, 12:45 a.m.)
Deposited	6 months ago (Feb. 22, 2025, 3:48 p.m.)
Indexed	3 weeks, 1 day ago (Aug. 2, 2025, 12:23 a.m.)
Issued	28 years, 7 months ago (Jan. 1, 1997)
Published	28 years, 7 months ago (Jan. 1, 1997)
Published Online	16 years, 7 months ago (Dec. 31, 2008)
Published Print	28 years, 7 months ago (Jan. 1, 1997)

Funders 5

National Cancer Institute 10.13039/100000054
Region: Americas
gov (National government)
Labels4
1. Instituto Nacional del Cáncer
2. National Cancer Institute at the National Institutes of Health
3. Instituto Nacional del Cáncer de los Institutos Nacionales de la Salud
4. NCI
Awards1
1. l-CO-74102
DHHS
BSF
Awards1
1. 95-00208
Israel Academy of Sciences
Rekanati Fund

BibTeX

@article{Tsai_1997, title={Studies of protein‐protein interfaces: A statistical analysis of the hydrophobic effect}, volume={6}, ISSN={1469-896X}, url={http://dx.doi.org/10.1002/pro.5560060106}, DOI={10.1002/pro.5560060106}, number={1}, journal={Protein Science}, publisher={Wiley}, author={Tsai, Chung‐Jung and Lin, Shuo Liang and Wolfson, Haim J. and Nussinov, Ruth}, year={1997}, month=jan, pages={53–64} }

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