An exact algorithm for side-chain placement in protein design

作者：Canzar Stefan; Toussaint Nora C; Klau Gunnar W^*

来源：Optimization Letters, 2011, 5(3): 393-406.

DOI：10.1007/s11590-011-0308-0

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

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 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.

• 出版日期2011-8
• 单位上海生物信息技术研究中心