期刊
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
卷 16, 期 10, 页码 6586-6597出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jctc.0c00305
关键词
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资金
- Spanish Ministry of Science [RTI2018-096704-B-100]
- Catalan SGR
- Biomolecular and Bioinformatics Resources Platform [ISCIII PT 13/0001/0030]
- Fondo Europeo de Desarrollo Regional (FEDER)
- MINECO Severo Ochoa Award of Excellence (Government of Spain)
- CDTI (Neotec) [EXP 00094141/SNEO-20161127]
- Fundacio'n Boti'n (Mind the Gap Program)
- Horizon 2020 Research and Innovation Programme of the European Union under the Marie Sklodowska-Curie Grant [752415]
- BSC
- European Union's Horizon 2020 research and innovation program [BioExcel-2 project]
- Marie Curie Actions (MSCA) [752415] Funding Source: Marie Curie Actions (MSCA)
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 of the steps to transform one-dimensional (1D) or 2D representation of drugs into 3D 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 are 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
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