TY - JOUR
T1 - Protein functional epitopes
T2 - Hot spots, dynamics and combinatorial libraries
AU - Ma, Buyong
AU - Wolfson, Haim J.
AU - Nussinov, Ruth
N1 - Funding Information:
We thank JV Maizel for discussions and for encouragement. We thank our students Tal Elkayam and Maxim Shatsky for generating Fig. 1 and Fig. 2 , respectively. M Shatsky has written the program used for creating the alignment in Fig. 2 . The research of R Nussinov and HJ Wolfson in Israel has been supported in part by the Magnet grant, by the Ministry of Science grant, and by the ‘Center of Excellence in Geometric Computing and its Applications’ funded by the Israel Science Foundation (administered by the Israel Academy of Sciences). The research of HJ Wolfson is partially supported by the Hermann Minkowski-Minerva Center for Geometry at Tel Aviv University. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number NO1-CO-56000. The content of this publication does not necessarily reflect the view or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the US Government.
PY - 2001/6/1
Y1 - 2001/6/1
N2 - Recent studies increasingly point to the importance of structural flexibility and plasticity in proteins, highlighting the evolutionary advantage. There are an increasing number of cases in which given, presumably specific, binding sites have been shown to bind a range of ligands with different compositions and shapes. These studies have also revealed that evolution tends to find convergent solutions for stable intermolecular associations, largely via conservation of polar residues as hot spots of binding energy. On the other hand, the ability to bind multiple ligands at a given site is largely derived from hinge-based motions. The consideration of these two factors in functional epitopes allows more realism and robustness in the description of protein binding surfaces and, as such, in applications to mutants, modeled structures and design. Efficient multiple structure comparison and hinge-bending structure comparison tools enable the construction of combinatorial binding epitope libraries.
AB - Recent studies increasingly point to the importance of structural flexibility and plasticity in proteins, highlighting the evolutionary advantage. There are an increasing number of cases in which given, presumably specific, binding sites have been shown to bind a range of ligands with different compositions and shapes. These studies have also revealed that evolution tends to find convergent solutions for stable intermolecular associations, largely via conservation of polar residues as hot spots of binding energy. On the other hand, the ability to bind multiple ligands at a given site is largely derived from hinge-based motions. The consideration of these two factors in functional epitopes allows more realism and robustness in the description of protein binding surfaces and, as such, in applications to mutants, modeled structures and design. Efficient multiple structure comparison and hinge-bending structure comparison tools enable the construction of combinatorial binding epitope libraries.
UR - http://www.scopus.com/inward/record.url?scp=0035366379&partnerID=8YFLogxK
U2 - 10.1016/S0959-440X(00)00216-5
DO - 10.1016/S0959-440X(00)00216-5
M3 - סקירה
AN - SCOPUS:0035366379
VL - 11
SP - 364
EP - 369
JO - Current Opinion in Structural Biology
JF - Current Opinion in Structural Biology
SN - 0959-440X
IS - 3
ER -