2010/01/15 by Jan Fuhrmann, Alexander Rurainski, Hans‐Peter Lenhof +1
Computer Science · Chemistry · #Computational Drug Discovery Methods #Synthesis and Biological Evaluation #Click Chemistry and Applications
paper · pdf · doi:10.1002/jcc.21478
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 docking. 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.