Interdomain Dynamics via Paramagnetic NMR on the Highly Flexible Complex Calmodulin/Munc13-1

• DOI: 10.1021/jacs.2c06611
• Publication Date: 2022-09-09T20:53:37Z
• Authors: Niels Karschin; Stefan Becker; Christian Griesinger
• Keywords: Dynamics; Residual dipolar coupling

Paramagnetic NMR constraints are very useful to study protein interdomain motion, but their interpretation is not always straightforward. On the example of particularly flexible complex Calmodulin/Munc13-1, we present a new approach characterize this motion with pseudocontact shifts and residual dipolar couplings. Using molecular mechanics, sampled conformational space used genetic algorithm find ensembles that in agreement data. We Bayesian information criterion determine ideal ensemble size. This way, were able make an accurate, unambiguous, reproducible model Calmodulin/Munc13-1 without prior knowledge about domain orientation from crystallography.