NMR Relaxation in Proteins with Fast Internal Motions and Slow Conformational Exchange: Model-Free Framework and Markov State Simulations

Junchao Xia, Nan-jie Deng, Ronald M. Levy
2013 Journal of Physical Chemistry B  
Calculating NMR relaxation effects for proteins with dynamics on multiple timescales generally requires very long trajectories based on conventional molecular dynamics simulations. In this report, we have built Markov state models from multiple MD trajectories and used the resulting MSM to capture the very fast internal motions of the protein within a free energy basin on a time scale up to hundreds of picoseconds and the more than three orders of magnitude slower conformational exchange
more » ... macrostates. To interpret the relaxation data, we derive new equations using the model free framework which includes two slowly exchanging macrostates, each of which also exhibits fast local motions.. Using simulations of HIV-1 Protease as an example, we show how the populations of slowly exchanging conformational states as well as order parameters for the different states can be determined from the NMR relaxation data. . Supporting Information Available Details about the building of the Markov state kinetic network, the NMR theory and the derivation of two-state exchange model with fast internal motions, and the calculation of NMR quantities from the trajectories have been included in the supporting information. This material is available free of charge via the Internet at
doi:10.1021/jp400797y pmid:23638941 pmcid:PMC3727231 fatcat:gtdo4vxbp5gpxh4kqzka6fiig4