A New Lamarckian Genetic Algorithm for Flexible Ligand-Receptor Docking

作者：Fuhrmann Jan; Rurainski Alexander; Lenhof Hans Peter; Neumann Dirk^*

来源：Journal of Computational Chemistry, 2010, 31(9): 1911-1918.

DOI：10.1002/jcc.21478

• meta-heuristic
• ligand-receptor docking
• unconstrained minimization
• gradient based minimization

We present a Lamarckian genetic algorithm (LGA) variant for flexible ligand-receptor docking which allows to handle a large number of degrees of freedom. Our hybrid method combines a multi-deme LGA with a recently published gradient-based method for local optimization of molecular complexes. We compared the performance of our new hybrid method to two non gradient-based search heuristics on the Astex diverse set for flexible ligand-receptor clocking. Our results show that the novel approach is clearly superior to other LGAs employing a stochastic optimization method. The new algorithm features a shorter run time and gives substantially better results, especially with increasing complexity of the ligands. Thus, it may be used to dock ligands with many rotatable bonds with high efficiency.

• 出版日期2010-7-15
• 单位上海生物信息技术研究中心