TY - JOUR
T1 - Molecular recognition via face center representation of a molecular surface
AU - Lin, Shuo Liang
AU - Nussinov, Ruth
N1 - Funding Information:
We thank Drs. Jacob Maizel and Haim Wolfson lor helpful discussions, encouragement, and interest. We thank the personnel at the Frederick Cancer Research and Development Center for their assistance. The research of R. Nussinov has been sponsored by the National Cancer Institute, DHHS, under Contract No. 1-CO-74102 with Scientific Application International Co., and in part by Grant No. 91-00219 from the U.S.-lsrael Binational Science Foundation (BSF) (Jerusalem, Israel) and by a grant from the Israel Science Foundation administered by the Israel Academy of Sciences. The contents of this publication do not necessarily reflect the views or policies of the DHHS, nor does mention of trade names, commercial products, or organization imply endorsement b) the U.S. Government.
PY - 1996/4
Y1 - 1996/4
N2 - While docking methodologies are now frequently being developed, a careful examination of the molecular surface representation, which necessarily is employed by them, is largely overlooked. There are two important aspects here that need to be addressed: how the surface representation quantifies surface complementarity and whether a minimal representation is employed. Although complementarity is an accepted concept regarding molecular recognition, its quantification for computation is not trivial, and requires verification. A minimal representation is important because docking searches a conformational space whose extent and/or dimensionality grows quickly with the size of surface representation, making it especially costly with big molecules, imperfect interfaces, and changes of conformation that occur in binding. It is essential for a docking methodology to establish that it employs an accurate, concise molecular surface representation. Here we employ the face center representation of molecular surface, developed by Lin et al., to investigate the complementarity of molecular interface. We study a wide variety of complexes: protein/small ligand, oligomeric chain-chain interfaces, proteinase/protein inhibitors, antibody/antigen, NMR structures, and complexes built from unbound, separately solved structures. The complementarity is examined at different levels of reduction, and hence roughness, of the surface representation, from one that describes subatomic details to a very sparse one that captures only the prominent features on the surface. Our simulation of molecular recognition indicates that in all cases, quality interface complementarity is obtained. We show that the representation is powerful in monitoring the complementarity either in its entirety, or in selected subsets that maintain a fraction of the face centers, and is capable of supporting molecular docking at high fidelity and efficiency. Furthermore, we also demonstrate that the presence of explicit hydrogens in molecular structures may not benefit docking, and that the different classes of protein complexes may hold slightly different degrees of interface complementarity.
AB - While docking methodologies are now frequently being developed, a careful examination of the molecular surface representation, which necessarily is employed by them, is largely overlooked. There are two important aspects here that need to be addressed: how the surface representation quantifies surface complementarity and whether a minimal representation is employed. Although complementarity is an accepted concept regarding molecular recognition, its quantification for computation is not trivial, and requires verification. A minimal representation is important because docking searches a conformational space whose extent and/or dimensionality grows quickly with the size of surface representation, making it especially costly with big molecules, imperfect interfaces, and changes of conformation that occur in binding. It is essential for a docking methodology to establish that it employs an accurate, concise molecular surface representation. Here we employ the face center representation of molecular surface, developed by Lin et al., to investigate the complementarity of molecular interface. We study a wide variety of complexes: protein/small ligand, oligomeric chain-chain interfaces, proteinase/protein inhibitors, antibody/antigen, NMR structures, and complexes built from unbound, separately solved structures. The complementarity is examined at different levels of reduction, and hence roughness, of the surface representation, from one that describes subatomic details to a very sparse one that captures only the prominent features on the surface. Our simulation of molecular recognition indicates that in all cases, quality interface complementarity is obtained. We show that the representation is powerful in monitoring the complementarity either in its entirety, or in selected subsets that maintain a fraction of the face centers, and is capable of supporting molecular docking at high fidelity and efficiency. Furthermore, we also demonstrate that the presence of explicit hydrogens in molecular structures may not benefit docking, and that the different classes of protein complexes may hold slightly different degrees of interface complementarity.
KW - Complementarity
KW - Docking
KW - Molecular recognition
KW - Molecular shape
KW - Surface representation
UR - http://www.scopus.com/inward/record.url?scp=0030130449&partnerID=8YFLogxK
U2 - 10.1016/0263-7855(96)00030-6
DO - 10.1016/0263-7855(96)00030-6
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AN - SCOPUS:0030130449
SN - 0263-7855
VL - 14
SP - 78
EP - 90
JO - Journal of Molecular Graphics
JF - Journal of Molecular Graphics
IS - 2
ER -