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Chapitre D'ouvrage Année : 2024

Molecular Dynamics as a Tool for Virtual Ligand Screening

Résumé

Rational drug design is essential for new drugs to emerge, especially when the structure of a target protein or nucleic acid is known. To that purpose, high-throughput virtual ligand screening campaigns aim at discovering computationally new binding molecules or fragments to modulate particular biomolecular interactions or biological activities, related to a disease process. The structure-based virtual ligand screening process primarily relies on docking methods which allow predicting the binding of a molecule to a biological target structure with a correct conformation and the best possible affinity. The docking method itself is not sufficient as it suffers from several and crucial limitations (lack of full protein flexibility information, no solvation and ion effects, poor scoring functions, and unreliable molecular affinity estimation).At the interface of computer techniques and drug discovery, molecular dynamics (MD) allows introducing protein flexibility before or after a docking protocol, refining the structure of protein-drug complexes in the presence of water, ions, and even in membrane-like environments, describing more precisely the temporal evolution of the biological complex and ranking these complexes with more accurate binding energy calculations. In this chapter, we describe the up-to-date MD, which plays the role of supporting tools in the virtual ligand screening (VS) process.Without a doubt, using docking in combination with MD is an attractive approach in structure-based drug discovery protocols nowadays. It has proved its efficiency through many examples in the literature and is a powerful method to significantly reduce the amount of required wet experimentations.
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Dates et versions

hal-04258325 , version 1 (25-10-2023)

Identifiants

Citer

Grégory Menchon, Laurent Maveyraud, Georges Czaplicki. Molecular Dynamics as a Tool for Virtual Ligand Screening. Computational Drug Discovery and Design, 2714, pp.33-83, 2024, Methods in Molecular Biology, ⟨10.1007/978-1-0716-3441-7_3⟩. ⟨hal-04258325⟩
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