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Ensemble-based docking: From hit discovery to metabolism and toxicity predictions.
Evangelista, Wilfredo; Weir, Rebecca L; Ellingson, Sally R; Harris, Jason B; Kapoor, Karan; Smith, Jeremy C; Baudry, Jerome.
Afiliação
  • Evangelista W; Department of Biochemistry and Cellular and Molecular Biology, The University of Tennessee, Knoxville, TN, United States; UT/ORNL Center for Molecular Biophysics, Oak Ridge National Laboratory, Oak Ridge, TN, United States.
  • Weir RL; Department of Biochemistry and Cellular and Molecular Biology, The University of Tennessee, Knoxville, TN, United States; UT/ORNL Center for Molecular Biophysics, Oak Ridge National Laboratory, Oak Ridge, TN, United States.
  • Ellingson SR; UT/ORNL Center for Molecular Biophysics, Oak Ridge National Laboratory, Oak Ridge, TN, United States; Genome Science and Technology, University of Tennessee, Knoxville, TN, United States; Division of Biomedical Informatics, College of Medicine, University of Kentucky and Cancer Research Informatics,
  • Harris JB; UT/ORNL Center for Molecular Biophysics, Oak Ridge National Laboratory, Oak Ridge, TN, United States; Genome Science and Technology, University of Tennessee, Knoxville, TN, United States.
  • Kapoor K; UT/ORNL Center for Molecular Biophysics, Oak Ridge National Laboratory, Oak Ridge, TN, United States; Genome Science and Technology, University of Tennessee, Knoxville, TN, United States.
  • Smith JC; Department of Biochemistry and Cellular and Molecular Biology, The University of Tennessee, Knoxville, TN, United States; UT/ORNL Center for Molecular Biophysics, Oak Ridge National Laboratory, Oak Ridge, TN, United States; Genome Science and Technology, University of Tennessee, Knoxville, TN, Unite
  • Baudry J; Department of Biochemistry and Cellular and Molecular Biology, The University of Tennessee, Knoxville, TN, United States; UT/ORNL Center for Molecular Biophysics, Oak Ridge National Laboratory, Oak Ridge, TN, United States; Genome Science and Technology, University of Tennessee, Knoxville, TN, Unite
Bioorg Med Chem ; 24(20): 4928-4935, 2016 10 15.
Article em En | MEDLINE | ID: mdl-27543390
This paper describes and illustrates the use of ensemble-based docking, i.e., using a collection of protein structures in docking calculations for hit discovery, the exploration of biochemical pathways and toxicity prediction of drug candidates. We describe the computational engineering work necessary to enable large ensemble docking campaigns on supercomputers. We show examples where ensemble-based docking has significantly increased the number and the diversity of validated drug candidates. Finally, we illustrate how ensemble-based docking can be extended beyond hit discovery and toward providing a structural basis for the prediction of metabolism and off-target binding relevant to pre-clinical and clinical trials.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Preparações Farmacêuticas / Descoberta de Drogas / Simulação de Acoplamento Molecular Tipo de estudo: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Bioorg Med Chem Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Preparações Farmacêuticas / Descoberta de Drogas / Simulação de Acoplamento Molecular Tipo de estudo: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Bioorg Med Chem Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos