TY - JOUR
T1 - Protein structure prediction via combinatorial assembly of sub-structural units
AU - Inbar, Yuval
AU - Benyamini, Hadar
AU - Nussinov, Ruth
AU - Wolfson, Haim J.
N1 - Funding Information:
This research has been supported in part by the ‘Center of Excellence in Geometric Computing and its Applications’ funded by the Israel Science Foundation (administered by the Israel Academy of Sciences) and by grants of Tel-Aviv University Basic Research Foundation. The research of H.J. Wolfson has been partially supported by the Hermann Minkowski-Minerva Center for Geometry at Tel Aviv University. The research of H. Benyamini has been supported by the Eshkol Fellowship funded by the Israeli Ministry of Science. The research of R. Nussinov 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-12400. 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 U.S. Government.
PY - 2003
Y1 - 2003
N2 - Following the hierarchical nature of protein folding, we propose a three-stage scheme for the prediction of a protein structure from its sequence. First, the sequence is cut to fragments that are each assigned a structure. Second, the assigned structures are combinatorially assembled to form the overall 3D organization. Third, highly ranked predicted arrangements are completed and refined. This work focuses on the second stage of this scheme: the combinatorial assembly. We present CombDock, a combinatorial docking algorithm. CombDock gets an ordered set of protein sub-structures and predicts the inter-contacts that define their overall organization. We reduce the combinatorial assembly to a graph-theory problem, and give a heuristic polynomial solution to this computationally hard problem. We applied CombDock to various examples of structural units of two types: protein domains and building flocks, which are relatively stable sub-structures of domains. Moreover, we tested CombDock using increasingly distorted input, where the native structural units were replaced by similarly folded units extracted from homologous proteins and, in the more difficult cases, from globally unrelated proteins. The algorithm is robust, showing low sensitivity to input distortion. This suggests that CombDock is a useful tool in protein structure prediction that may be applied to large target proteins. Supplementary information: More tables and figures are available at www.cs.tau.ac.il/~inbaryuv/combdock/.
AB - Following the hierarchical nature of protein folding, we propose a three-stage scheme for the prediction of a protein structure from its sequence. First, the sequence is cut to fragments that are each assigned a structure. Second, the assigned structures are combinatorially assembled to form the overall 3D organization. Third, highly ranked predicted arrangements are completed and refined. This work focuses on the second stage of this scheme: the combinatorial assembly. We present CombDock, a combinatorial docking algorithm. CombDock gets an ordered set of protein sub-structures and predicts the inter-contacts that define their overall organization. We reduce the combinatorial assembly to a graph-theory problem, and give a heuristic polynomial solution to this computationally hard problem. We applied CombDock to various examples of structural units of two types: protein domains and building flocks, which are relatively stable sub-structures of domains. Moreover, we tested CombDock using increasingly distorted input, where the native structural units were replaced by similarly folded units extracted from homologous proteins and, in the more difficult cases, from globally unrelated proteins. The algorithm is robust, showing low sensitivity to input distortion. This suggests that CombDock is a useful tool in protein structure prediction that may be applied to large target proteins. Supplementary information: More tables and figures are available at www.cs.tau.ac.il/~inbaryuv/combdock/.
KW - Combinatorial assembly
KW - Hierarchical model
KW - Multiple docking
KW - Structure prediction
UR - http://www.scopus.com/inward/record.url?scp=2942552020&partnerID=8YFLogxK
U2 - 10.1093/bioinformatics/btg1020
DO - 10.1093/bioinformatics/btg1020
M3 - מאמר
C2 - 12855452
AN - SCOPUS:2942552020
VL - 19
SP - i158-i168
JO - Bioinformatics
JF - Bioinformatics
SN - 1367-4803
IS - SUPPL. 1
ER -