Determination of accurate structural models of proteins or oligonucleotides exhibiting conformational flexibility is a major challenge for any experimental biophysical technique owing to a large number of degrees of freedom necessary, compared to the number of available experimental restraints. In this project we aim to maximally regularize the derived ensemble of models by determining multi-dimensional probability distribution functions of the relevant structural parameters using solution NMR combined with X-ray and neutron scattering. The methodology will initially be applied to a number of proteins exhibiting flexible inter-domain linkages and/or mobile internal regions, as well as RNA and DNA constructs with high density of residual dipolar coupling (RDC) restraints.

 

Reference

Maltsev AS, Grishaev A, et al: Improved cross-validation of a static ubiquitin structure derived from high precision residual dipolar couplings measured in a drug-based liquid crystalline phase. Journal of the American Chemical Society 136: 3752-3755, 2014

 

key words

Protein and RNA flexibility and dynamics; NMR; Solution scattering; Structural biology; SAXS; SANS; Residual dipolar coupling (RDC);

Citizenship:  Open to U.S. citizens

Level:  Open to Postdoctoral applicants