Thermal Titration Molecular Dynamics: The Revenge of the Fragments.

ABSTRACT: During the last 20 years, the fragment-based drug discovery approach gained popularity in both industrial and academic settings due to its efficient exploration of the chemical space. This bottom-up approach relies on identifying high-efficiency small ligands (fragments) that bind to a target binding site and then rationally evolve them into mature druglike compounds. To achieve such a task, researchers rely on accurate information about the ligand binding mode, usually obtained through experimental techniques, such as X-ray crystallography or computer simulations. However, the physicochemical characteristics of fragments limit the accuracy and reliability of computational predictions of their binding mode. This article presents a new Thermal Titration Molecular Dynamics (TTMD) protocol, a

SUBMITTER: Pavan M 

PROVIDER: S-EPMC11815869 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature