TY - JOUR
T1 - Protein-protein interactions
T2 - Coupling of structurally conserved residues and of hot spots across interfaces. Implications for docking
AU - Halperin, Inbal
AU - Wolfson, Haim
AU - Nussinov, Ruth
N1 - Funding Information:
We thank Ozlem Keskin for generously sharing the interfaces data base. We particularly thank Dina Schneidman for carrying out the docking experiments and for her invaluable advice. We thank Amir Beck for excellent statistical consultation. We thank Dr. Buyong Ma for many helpful discussions. The research of R.N. and H.W. in Israel has been supported in part by the Center of Excellent in Geometric Computing and its Applications, funded by the Israel Science Foundation (administered by the Israel Academy of Sciences). The research of H.J.W. is partially supported by the Hermann Minkowsky-Minerva Center for Geometry at Tel-Aviv University. This project has been funded in whole or in part with Federal funds from the National Canter Institute of Health, under contract number NO1-CO-12400. The content of this publication does not necessarily reflect the view or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organization imply endorsement by the U.S. government. The publisher or recipient acknowledges the right of the U.S. government to retain a nonexclusive, royalty-free license in and to any copyright covering the article. This work was performed in partial fulfillment of the requirements for a Ph.D. degree of Inbal Halperin, Sackler Faculty of Molecular Medicine, Tel-Aviv University, Israel.
PY - 2004/6
Y1 - 2004/6
N2 - Hot spot residues contribute dominantly to protein-protein interactions. Statistically, conserved residues correlate with hot spots, and their occurrence can distinguish between binding sites and the remainder of the protein surface. The hot spot and conservation analyses have been carried out on one side of the interface. Here, we show that both experimental hot spots and conserved residues tend to couple across two-chain interfaces. Intriguingly, the local packing density around both hot spots and conserved residues is higher than expected. We further observe a correlation between local packing density and experimental ΔΔG. Favorable conserved pairs include Gly coupled with aromatics, charged and polar residues, as well as aromatic residue coupling. Remarkably, charged residue couples are underrepresented. Overall, protein-protein interactions appear to consist of regions of high and low packing density, with the hot spots organized in the former. The high local packing density in binding interfaces is reminiscent of protein cores.
AB - Hot spot residues contribute dominantly to protein-protein interactions. Statistically, conserved residues correlate with hot spots, and their occurrence can distinguish between binding sites and the remainder of the protein surface. The hot spot and conservation analyses have been carried out on one side of the interface. Here, we show that both experimental hot spots and conserved residues tend to couple across two-chain interfaces. Intriguingly, the local packing density around both hot spots and conserved residues is higher than expected. We further observe a correlation between local packing density and experimental ΔΔG. Favorable conserved pairs include Gly coupled with aromatics, charged and polar residues, as well as aromatic residue coupling. Remarkably, charged residue couples are underrepresented. Overall, protein-protein interactions appear to consist of regions of high and low packing density, with the hot spots organized in the former. The high local packing density in binding interfaces is reminiscent of protein cores.
UR - http://www.scopus.com/inward/record.url?scp=2942553723&partnerID=8YFLogxK
U2 - 10.1016/j.str.2004.04.009
DO - 10.1016/j.str.2004.04.009
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C2 - 15274922
AN - SCOPUS:2942553723
SN - 0969-2126
VL - 12
SP - 1027
EP - 1038
JO - Structure
JF - Structure
IS - 6
ER -