Impact of receptor conformation on in silico screening performance

We report on results for the in silico screening of a database of 10 000 flexible compounds against various crystal structures of the thymidine kinase enzyme complexed with 10 known inhibitors. We provide a quantitative analysis of the deviations in the ranking of the inhibitors depending on the choice of receptor conformation and imply that the inclusion of side-chain degrees of freedom to the receptor would significantly improve the predictive power of the screening approach. We suggest a consensus score that, in the case of several known native structures of the receptor, enables the evaluation of scoring functions without the requirement of explicit receptor-flexibility.