Application of Drug-Perturbed Essential Dynamics/Molecular Dynamics (ED/MD) to Virtual Screening and Rational Drug Design

Autor:	Charles A. Laughton, Modesto Orozco, Oliver Carrillo, Rima Chaudhuri
Rok vydání:	2012
Předmět:	Quantitative Biology::Biomolecules Molecular dynamics Virtual screening Template Chemistry Docking (molecular) Computational chemistry A protein Drug design Physical and Theoretical Chemistry Biological system Small molecule Computer Science Applications
Zdroj:	Journal of Chemical Theory and Computation. 8:2204-2214
ISSN:	1549-9626 1549-9618
Popis:	We present here the first application of a new algorithm, essential dynamics/molecular dynamics (ED/MD), to the field of small molecule docking. The method uses a previously existing molecular dynamics (MD) ensemble of a protein or protein-drug complex to generate, with a very small computational cost, perturbed ensembles which represent ligand-induced binding site flexibility in a more accurate way than the original trajectory. The use of these perturbed ensembles in a standard docking program leads to superior performance than the same docking procedure using the crystal structure or ensembles obtained from conventional MD simulations as templates. The simplicity and accuracy of the method opens up the possibility of introducing protein flexibility in high-throughput docking experiments.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::72e9a0de8c94eb292b0ca0b96c661b13 https://doi.org/10.1021/ct300223c Zobrazit plný text záznamu