A Simple Method for Improving Torsion Optimization of Ligand Molecules in Receptor Binding Sites

A simple but effective method is introduced for optimizing ligand molecules in torsion space within receptor binding sites. The algorithm makes use of geometric constraints of ligand molecules to search for energetically favorable conformations. It is applied to a conjugate gradient (CG) method as an example. During conformational energy optimization, new line search directions are modified according to the spatial span of rotational groups in ligand molecules. Significant improvements were observed in terms of the abilities both to recover global optimal structures and to obtain lower energy ensembles. This simple algorithm allows rapid implementation and can be incorporated into other conformational energy optimization techniques.