Da-Wei Li, Ph.D.
Department of Chemistry and Biochemistry
Ohio State University

Host: Dr. David Koes

Synergies between NMR Chemical Shifts and Molecular Dynamics Simulations

Chemical shifts represent the most ubiquitous and accurately measured NMR parameters of proteins and their knowledge is a prerequisite for the interpretation of most NMR experiments. To date, chemical shifts of thousands of proteins have been deposited in the BioMagResDataBank. On the other hand, chemical shifts belong to the most difficult NMR parameters in terms of their interpretation because of their highly sensitive dependence on their local chemical environment. In addition, the experimental chemical shift of a given nucleus reflects the Boltzmann-weighted average of the ‘instantaneous’ chemical shifts of a large number of conformational sub-states that interconvert on the millisecond timescale or faster, which are hard to capture. Chemical shift information has found widespread use in protein NMR, such as for the assessment of the propensity of protein segments to adopt various types of secondary structure, the determination and refinement of 3D protein structures, and the extraction of site-specific order parameters as measures of local dynamics. In this talk, I will discuss some of our recent work from two sides of the protein chemical shift problem: (1) the prediction of chemical shifts through in silico protein ensembles and (2) the improvement of molecular dynamics simulations through their protein force fields using experimental chemical shifts of native proteins as a guide.