Resolving Protein–Ligand Binding Pathways by NMR Relaxation | Prof. Mikael Akke | Session 108

Описание: During the 108th session of the Global NMR Discussion Meetings held on October 21st, 2025, via Zoom, Prof. Mikael Akke from the Lund University, Sweden, gave a talk on the topic "Resolving Protein–Ligand Binding Pathways by NMR Relaxation: Conformational Selection vs Induced Fit". The recording serves as a tutorial.

Find out more about Prof. Mikael Akke's research :
https://portal.research.lu.se/en/pers...

Abstract:
Protein–ligand binding is essential for biological function. A long-standing question is whether ligand binding occurs via conformational selection (CS) or induced fit (IF). Using relaxation dispersion experiments with varying ligand concentration, we measured the 4-state binding kinetics encompassing both the CS and IF pathways in galectin-3. We determined the ligand affinity of each pathway, all rate constants and populations, and the relative flux through each pathway — all of which provide a very rich understanding of protein–ligand binding and some surprising results.

Content of this video :
00:00 - 07:31 Introducing ligand binding and the model system
07:32 - 16:31 How can comformational exchange be studied with NMR ?
16:32 - 31:31 Experimental measurements and examples
31:32 - 38:31 Using simulations to determine exchange rates
38:32 - 44:26 Determine which pathway dominates
44:27 - 01:08:42 Q&A

Current organizers:
Adrian Draney (Creighton Uni.)
Amrit Venkatesh (University of Virginia)
Asif Equbal (New York Uni., Abu Dhabi)
Charlotte Bocquelet (HMRLab, CRMN Lyon)
Diganta Sarkar (Alberta Uni.)
Julie Buhl (Uni. JKU Linz)
Marcel Levien (Emsley Lab, EPFL)
Mengshan Ye (Miller Institute, UC Berkeley)
Mouzhe Xie (Arizona State Uni.)
Nikita Rao (Indian Institute of Science, Bangalore)
Nesreen Elathram (Debelouchina Lab, UCSD)
Tamali Nag (Uni. of Lille/Grenoble)