An exact algorithm for side-chain placement in protein design


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 (SCP) problem consists of choosing a SCP 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 \({\mathcal{NP}}\)-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 SCP 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 SCP. 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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Correspondence to Gunnar W. Klau.

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Canzar, S., Toussaint, N.C. & Klau, G.W. An exact algorithm for side-chain placement in protein design. Optim Lett 5, 393–406 (2011).

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  • Lagrangian relaxation
  • Branch-and-bound
  • Algorithm engineering
  • Protein design
  • side-chain placement