Structure-based calculation of drug efficiency indices
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 me...
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| Veröffentlicht in: | Bioinformatics 2007-10, Vol.23 (20), p.2678-2685 |
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| creator | Hetényi, Csaba Maran, Uko García-Sosa, Alfonso T. Karelson, Mati |
| description | 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 β-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. Contact: csabahete@yahoo.com Supplementary information: Accompanies this manuscript on the publisher's web site. |
| doi_str_mv | 10.1093/bioinformatics/btm431 |
| format | Article |
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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 β-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. 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| subjects | Binding Sites Biological and medical sciences Computer Simulation Drug Design Drug Evaluation, Preclinical - methods Fundamental and applied biological sciences. Psychology General aspects Mathematics in biology. Statistical analysis. Models. Metrology. Data processing in biology (general aspects) Models, Chemical Models, Molecular Pharmaceutical Preparations - chemistry Protein Binding Proteins - chemistry Proteins - ultrastructure |
| title | Structure-based calculation of drug efficiency indices |
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