Boosting drug discovery: expanding the applicability of fragment dissolved molecular dynamics to accelerate binding mode elucidation
The use of small organic molecules has become one of the most popular strategies in computer-aided drug design (CADD) to facilitate the identification of potential drug-like compounds in the early stages of drug development. In this scenario, novel computational approaches such as the use of the fra...
| Autores: | , , , |
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| Tipo de documento: | artigo |
| Data de publicação: | 2025 |
| País: | España |
| Recursos: | Universitat Politècnica de Catalunya (UPC) |
| Repositório: | UPCommons. Portal del coneixement obert de la UPC |
| Idioma: | inglês |
| OAI Identifier: | oai:upcommons.upc.edu:2117/458961 |
| Acesso em linha: | https://hdl.handle.net/2117/458961 https://dx.doi.org/10.1021/acs.jcim.5c02122 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Molecular dynamics Drugs Computational chemistry Drug discovery Ligands Screening assays Dinàmica molecular Medicaments Àrees temàtiques de la UPC::Enginyeria biomèdica |
| Resumo: | The use of small organic molecules has become one of the most popular strategies in computer-aided drug design (CADD) to facilitate the identification of potential drug-like compounds in the early stages of drug development. In this scenario, novel computational approaches such as the use of the fragment dissolved molecular dynamics (fdMD) methodology emerged as a new framework for the modeling of ligand–receptor interactions. Consisting of molecular dynamics (MD) simulations of the target protein solvated with multiple copies of the same fragment, the original approach is able to identify the most favorable binding site for the system studied in a reasonable simulation time scale (0.2–1 µs). In the present work, we have introduced the use of Gaussian accelerated molecular dynamics (GaMD) to facilitate system exploration, accelerate binding site identification and additionally enhance binding mode elucidation. For this purpose, up to 12 different systems with crystallographic information available have been employed for validation. |
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