Fast Validation of Static and Dynamic 3D Models of Weak Protein Ligand Complexes from STD NMR Spectroscopy

Abstract

Saturation transfer difference NMR spectroscopy has revolutionized the study of weak receptor-ligand interactions. Its versatility and popularity are demonstrated by a myriad of approaches developed. Methodologies such as DEEP STD NMR, KD determination, SSTD, and determination and validation of protein-ligand complexes are a few elegant examples among them. However, the use of the STD NMR technique together with full relaxation matrix calculations for the determination and structure evaluation of protein ligand complexes remain a major milestone in the field. In this communication, we present a new approach based on a reduced relaxation matrix that pushes further the boundaries of the relaxation matrix theory applied to structure determination and evaluation, in solution, using STD NMR data and molecular dynamics simulations.