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Integrating Molecular Docking and Molecular Dynamics Simulations

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Docking Screens for Drug Discovery

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2053))

Abstract

Computational methods, applied at the early stages of the drug design process, use current technology to provide valuable insights into the understanding of chemical systems in a virtual manner, complementing experimental analysis. Molecular docking is an in silico method employed to foresee binding modes of small compounds or macromolecules in contact with a receptor and to predict their molecular interactions. Moreover, the methodology opens up the possibility of ranking these compounds according to a hierarchy determined using particular scoring functions. Docking protocols assign many approximations, and most of them lack receptor flexibility. Therefore, the reliability of the resulting protein–ligand complexes is uncertain. The association with the costly but more accurate MD techniques provides significant complementary with docking. MD simulations can be used before docking since a series of “new” and broader protein conformations can be extracted from the processing of the resulting trajectory and employed as targets for docking. They also can be utilized a posteriori to optimize the structures of the final complexes from docking, calculate more detailed interaction energies, and provide information about the ligand binding mechanism. Here, we focus on protocols that offer the docking–MD combination as a logical approach to improving the drug discovery process.

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Authors and Affiliations

  1. Laboratório de Modelagem Molecular e Planejamento de Fármacos, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

    Lucianna H. S. Santos

  2. Laboratório de Modelagem Molecular e Planejamento de Fármacos, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

    Rafaela S. Ferreira

  3. Programa de Computação Científica, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil

    Ernesto R. Caffarena

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  1. Lucianna H. S. Santos
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  2. Rafaela S. Ferreira
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  3. Ernesto R. Caffarena
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Correspondence to Ernesto R. Caffarena .

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  1. Escola de Ciências da Saúde, Pontifícia Universidade Católica do Rio Grande do Sul—PUCRS, Porto Alegre, Rio Grande do Sul, Brazil

    Walter Filgueira de Azevedo Jr.

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Santos, L.H.S., Ferreira, R.S., Caffarena, E.R. (2019). Integrating Molecular Docking and Molecular Dynamics Simulations. In: de Azevedo Jr., W. (eds) Docking Screens for Drug Discovery. Methods in Molecular Biology, vol 2053. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9752-7_2

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  • DOI: https://doi.org/10.1007/978-1-4939-9752-7_2

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