title: Structure-based calculation of drug efficiency indices.
abstract: BACKGROUND
  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.
  
  
  BACKGROUND
  Accompanies this manuscript on the publisher's web site.
authors.affiliation: Institute of Chemical Physics, University of Tartu, 2 Jakobi Street, 51014 Tartu, Estonia. csabahete@yahoo.com
authors.forename: Csaba
authors.initials: C
authors.lastname: Hetényi
authors.forename: Uko
authors.initials: U
authors.lastname: Maran
authors.forename: Alfonso T
authors.initials: AT
authors.lastname: García-Sosa
authors.forename: Mati
authors.initials: M
authors.lastname: Karelson
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D008956:Models, Chemical; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000648:ultrastructure*