Motivation: The efficiency indices (EI's) have been derived from the experimental binding affinities of drug candidates to macromolecules. These 'two-in-one' measures include information on both pharmacodynamics and pharmacokinetics of the candidate molecules. The time-consuming experimental measurement of binding affinities of extensive molecule libraries may become a bottle-neck of large scale generation and application of EI's.
Results: To overcome this limitation, structure-based calculation of new EI's is introduced using the modified free energy function of the popular program package AutoDock. The results are validated on experimental binding data of biochemical systems such as potent inhibitors bound to beta-secretase, a key enzyme of Alzheimer's disease and various drug-protein complexes. Application of new EI's is tested. Thermodynamics of EI's and their role in virtual high-throughput screening of drugs and in the development of docking programs are discussed.
Supplementary information: Accompanies this manuscript on the publisher's web site.