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Communication Dans Un Congrès Année : 2021

NMR molecular replacement (NMR2) Structure determination of protein-ligand complexes

Résumé

Obtain the structural details of the protein-ligand structure is the key step to drive a rational drug design workflow in order to find novel inhibitors that can compete with those natural binders. Thus far, the most very well-known experimental methods to reach this goal are X-ray crystallography and NMR spectroscopy, which both present advantages and drawbacks. For example, several protein-ligand structures are not solvable by X-ray crystallography (e.g. in the cases of low affinity binders, dynamic proteins and/or large conformational changes upon binding). NMR in its counterpart, is very well suited for analyzing these kind of systems, but is limited by the often difficult task to assign all the atoms in the complex to their corresponding chemical shifts. Unfortunately, this very time-consuming task is necessary for the structure calculation procedure. In this project, we aim to develop methods to obtain a protein/ligand structure from NMR data without performing a detailed assignment of the protein, with the previous knowledge of the protein structure (apo, halo or homolog). The software CNS/ARIA will be used for the structure calculation and several new routines will be developed in order to implement new ideas in the context of the NMR2 project. We are also planning to integrate computational tools to consider protein flexibility and results of druggability studies, that could help to disambiguate the final results.

Domaines

Chimie
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Dates et versions

hal-04431477 , version 1 (01-02-2024)

Identifiants

  • HAL Id : hal-04431477 , version 1

Citer

Gauto Diego, Tarik Bekkour, Bontems François, Van-Heijenoort Carine, Martiny Virginie, et al.. NMR molecular replacement (NMR2) Structure determination of protein-ligand complexes. SEEDPODS 2021, Jun 2021, Suresnes, France. ⟨hal-04431477⟩
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