NMR relaxation – path to dynamics and entropy

Frans A. A. Mulder

Falk Hoffmann¹, Ahmed A.A.I. Ali¹, Mengjun Xue², Lars V. Schäfer¹, Frans A.A. Mulder²

1) Theoretical Chemistry, Ruhr University Bochum, D-44780 Bochum, Germany
2) Interdisciplinary Nanoscience Center (iNANO) and Department of Chemistry, Aarhus University, DK-8000 Aarhus, Denmark

While NMR nuclear spin relaxation is arguably the most comprehensive experimental approach to measure protein dynamics at atomic resolution, it is only highly approximate. MD simulation, on the other hand, describe molecular flexibility in amazing detail, but are heavily constrained by the accuracy of the molecular mechanics force field and conformational sampling. In my seminar I will take stock of the current state of affairs: (How) can NMR and MD be used synergistically to study the dynamics in proteins [1,4]. For example, MD simulations show that the most common and popular approach to interpret NMR data is highly inadequate [2]. Meanwhile, we have made good progress in decreasing gap between prediction and experiment, such that quantitative avenues for probing configurational entropy come into reach [3]. This is timely, as we cannot currently predict very simple things, such as the consequence of mutation on the stability of proteins in a rigorous thermodynamic way.

References: [1] Hoffmann F, Mulder FAA, Schäfer LV. J Phys Chem B. 2018, 122(19):5038-5048. [2] Hoffmann F, Xue M, Schäfer LV, Mulder FAA, Phys Chem Chem Phys. 2018, 20(38):24577-24590. [3] Hoffmann F, Mulder FAA, Schäfer LV. J Chem Phys. 2020, 152(8):084102. [4] Ali, AAI, Hoffmann F, Schäfer LV, Mulder FAA, J. Chem. Theory Comput., 2022, 18 (12):7722-7732.