Lessons Learned over Four Benchmark Exercises from the Community Structure-Activity Resource

Heather A. Carlson, Department of Medicinal Chemistry, United States, shares the lessons learnt from attending four CSAR (Community Stucture-Activity Resource) Benchmark Exercises. While attending the first exercise, he focused on identifying excellent crystal structures with really pristine electron density in the binding site. The structures were also required to have no contacts to the ligand from crystal additives or symmetry packing, so that any artificial deformation of the ligand coordinates could be avoided. He also learnt that several metrics are needed for assessing docking methods. The author is thoroughly convinced that the limited progress in scoring/ranking comes from ignoring statistics in our studies. There is no excuse for publishing results without some measure of error. It is best if the ligands in data sets span a large range of physical properties such as molecular weight, number of rotatable bonds, number of hydrogenbonding groups, etc. This allows developers to examine numerous factors that influence scoring.