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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/228773

Boosting Drug Discovery: Expanding the Applicability of Fragment Dissolved Molecular Dynamics to Accelerate Binding Mode Elucidation

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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 thefragment 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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PERALTA MORENO, María Nuria, et al. Boosting Drug Discovery: Expanding the Applicability of Fragment Dissolved Molecular Dynamics to Accelerate Binding Mode Elucidation. Journal of Chemical Information and Modeling. 2025. Vol. 65, núm. 23, pàgs. 12879-12893. ISSN 1549-9596. [consulta: 12 de maig de 2026]. Disponible a: https://hdl.handle.net/2445/228773

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