An Exact Algorithm for Side-Chain Placement in Protein Design

Stefan Canzar; Nora C. Toussaint; Gunnar W. Klau

doi:10.1007/s11590-011-0308-0

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arXiv · 1103.1503

An Exact Algorithm for Side-Chain Placement in Protein Design

Stefan Canzar·Nora C. Toussaint·Gunnar W. Klau

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Abstract

Computational protein design aims at constructing novel or improved functions on the structure of a given protein backbone and has important applications in the pharmaceutical and biotechnical industry. The underlying combinatorial side-chain placement problem consists of choosing a side-chain placement for each residue position such that the resulting overall energy is minimum. The choice of the side-chain then also determines the amino acid for this position. Many algorithms for this NP-hard problem have been proposed in the context of homology modeling, which, however, reach their limits when faced with large protein design instances. In this paper, we propose a new exact method for the side-chain placement problem that works well even for large instance sizes as they appear in protein design. Our main contribution is a dedicated branch-and-bound algorithm that combines tight upper and lower bounds resulting from a novel Lagrangian relaxation approach for side-chain placement. Our experimental results show that our method outperforms alternative state-of-the art exact approaches and makes it possible to optimally solve large protein design instances routinely.

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Stefan Canzar, Nora C. Toussaint, Gunnar W. Klau. 2011-03-08. An Exact Algorithm for Side-Chain Placement in Protein Design. https://doi.org/10.1007/s11590-011-0308-0

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