Protein structure prediction via combinatorial assembly of sub-structural units

Yuval Inbar*, Hadar Benyamini, Ruth Nussinov, Haim J. Wolfson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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

Original languageEnglish
Pages (from-to)i158-i168
Issue numberSUPPL. 1
StatePublished - 2003


FundersFunder number
Hermann Minkowski-MINERVA Center for Geometry
Israeli Ministry of Science
Tel-Aviv University Basic Research Foundation
National Institutes of HealthNO1-CO-12400
National Cancer InstituteZ01BC010442
Israel Academy of Sciences and Humanities
Israel Science Foundation
Tel Aviv University


    • Combinatorial assembly
    • Hierarchical model
    • Multiple docking
    • Structure prediction


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