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2020-08-06

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/179230

Bioactive conformational ensemble server and database. A public framework to speed up in silico drug discovery.

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https://doi.org/10.1021/acs.jctc.0c00305

Resum

Modern high-throughput structure-based drug discovery algorithms consider ligand flexibility, but typically with low accuracy, which results in a loss of performance in the derived models. Here we present the Bioactive Conformational Ensemble (BCE) server and its associated database. The server creates conformational ensembles of drug-like ligands and stores them in the BCE database, where a variety of analyses are offered to the user. The workflow implemented in the BCE server combines enhanced sampling molecular dynamics with self-consistent reaction field quantum mechanics (SCRF/QM) calculations. The server automatizes all the steps to transform 1D or 2D representation of drugs into three dimensional molecules, which are then titrated, parametrized, hydrated and optimized before being subjected to Hamiltonian replica-exchange (HREX) molecular dynamics simulations. Ensembles are collected and subjected to a clustering procedure to derive representative conformers, which are then analyzed at the SCRF/QM level of theory. All structural data is organized in a noSQL database accessible through a graphical interface and in a programmatic manner through a REST API. The server allows the user to define a private workspace and offers a deposition protocol as well as input files for "in house" calculations in those cases where confidentiality is a must. The database and the associated server are available at https://mmb.irbbarcelona.org/BCE

Matèries

Bases de dades, Molècules

Matèries (anglès)

Databases, Molecules

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Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

Citació

ZIVANOVIC, Sanja, BAYARRI, Genís, COLIZZI, Francesco, MORENO, David, GELPÍ BUCHACA, Josep lluís, SOLIVA, Robert, HOSPITAL GASCH, Adam, OROZCO LÓPEZ, Modesto. Bioactive conformational ensemble server and database. A public framework to speed up in silico drug discovery.. _Journal of Chemical Theory and Computation_. 2020. Vol. 16, núm. 10, pàgs. 6586-6597. [consulta: 20 de gener de 2026]. ISSN: 1549-9618. [Disponible a: https://hdl.handle.net/2445/179230]

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