TY - JOUR
T1 - An automated computer vision and roboticsbased technique for 3-D flexible biomolecular docking and matching
AU - Sandak, Bilha
AU - Nussinov, Ruth
AU - Wolfson, Haim J.
N1 - Funding Information:
We would like to thank A. Wlodawer for the coordinates of the HIV-1 protease-U-75875 inhibitor complex. We thank Drs. Shuo L. Lin, Robert Jernigan and Jacob Maizel, for helpful discussions, encouragement and interest. The research of R. Nussinov has been sponsored by the National Cancer Institute, DHHS, under Contract No. 1-CO-74102 with Program Resources, Inc. 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 of endorsement by the U.S. Government. The research of H.J. Wolfson has been supported in part by a grant from the Israel Science Foundation administered by the Israel Academy of Sciences, and by grant No. 83-00481 from the U.S.-Israel Binational Science Foundation (BSF), Jerusalem, Israel. The research of R. Nussinov in Israel has been supported in part by grant No. 91-00219 from the BSF, and by a grant from the Israel Science Foundation administered by the Israel Academy of Sciences. This work formed part of the Ph.D. Thesis of B. Sandak, Tel Aviv University.
PY - 1995/2
Y1 - 1995/2
N2 - The generation of binding modes between two molecules, also known as molecular docking, is a key problem in rational drug design and biomolecular recognition. Docking a ligand, e.g., a drug molecule or a protein molecule, to a protein receptor, involves recognition of molecular surfaces as molecules interact at their surface. Recent studies report that the activity of many molecules induces conformational transitions by 'hinge-bending', which involves movements of relatively rigid parts with respect to each other. In ligand-receptor binding, relative rotational movements of molecu-lar substructures about their common hinges have been observed. For automatically predicting flexible molecular interactions, we adapt a new technique developed in Computer Vision and Robotics for the efficient recognition of partially occluded articulated objects. These type of objects consist of rigid parts which are connected by rotary joints (hinges). Our approach is based on an extension and generalization of the Geometric Hashing and Generalized Hough Transform paradigm for rigid object recognition. Unlike other techniques which match each part individually, our approach exploits forcefully and efficiently enough the fact that the different rigid parts do belong to the same flexible molecule. We show experimental results obtained by an implementation of the algorithm for rigid and flexible docking. While the 'correct', crystal-bound complex is obtained with a small RMSD, additional, predictive 'high scoring' binding modes are generated as well. The diverse applications and implications of this general, powerful tool are discussed.
AB - The generation of binding modes between two molecules, also known as molecular docking, is a key problem in rational drug design and biomolecular recognition. Docking a ligand, e.g., a drug molecule or a protein molecule, to a protein receptor, involves recognition of molecular surfaces as molecules interact at their surface. Recent studies report that the activity of many molecules induces conformational transitions by 'hinge-bending', which involves movements of relatively rigid parts with respect to each other. In ligand-receptor binding, relative rotational movements of molecu-lar substructures about their common hinges have been observed. For automatically predicting flexible molecular interactions, we adapt a new technique developed in Computer Vision and Robotics for the efficient recognition of partially occluded articulated objects. These type of objects consist of rigid parts which are connected by rotary joints (hinges). Our approach is based on an extension and generalization of the Geometric Hashing and Generalized Hough Transform paradigm for rigid object recognition. Unlike other techniques which match each part individually, our approach exploits forcefully and efficiently enough the fact that the different rigid parts do belong to the same flexible molecule. We show experimental results obtained by an implementation of the algorithm for rigid and flexible docking. While the 'correct', crystal-bound complex is obtained with a small RMSD, additional, predictive 'high scoring' binding modes are generated as well. The diverse applications and implications of this general, powerful tool are discussed.
UR - http://www.scopus.com/inward/record.url?scp=0028940058&partnerID=8YFLogxK
U2 - 10.1093/bioinformatics/11.1.87
DO - 10.1093/bioinformatics/11.1.87
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AN - SCOPUS:0028940058
SN - 1367-4803
VL - 11
SP - 87
EP - 99
JO - Bioinformatics
JF - Bioinformatics
IS - 1
ER -