Fast Quantitative Validation of 3D Models of Low-Affinity Protein-Ligand Complexes by STD NMR Spectroscopy

11 July 2023, Version 2
This content is a preprint and has not undergone peer review at the time of posting.


Low-affinity protein-ligand interactions are important for many biological processes, including cell communication, signal transduction, and immune responses. Structural characterization of these complexes is also critical for the development of new drugs through fragment-based drug discovery (FBDD), but is challenging due to the low-affinity of fragments for the binding site. Saturation transfer difference (STD) NMR spectroscopy has revolutionized the study of low-affinity receptor-ligand interactions enabling binding detection and structural characterization. However, the use of the STD NMR technique together with full relaxation matrix calculations for the validation of 3D structures of protein-ligand complexes remains a major milestone in the field. In this work, we present a new approach based on a reduced relaxation matrix that allows very fast 3D structure evaluation of lowaffinity protein-ligand complexes by STD NMR data and molecular dynamics simulations.


Protein-ligand complex NMR validation
Weak affinity biomolecular interactions
Fragment based drug discovery

Supplementary materials

Fast Validation of 3D Protein-Ligand Complexes by STD NMR
Experimental and theoretical data, RedMat step-by-step user guide, Note about potential limitations.


Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.