Zerbetto, Mirco; Buck, Matthias; Meirovitch, Eva; Polimeno, Antonino
Integrated Computational Approach to the Analysis of NMR Relaxation in Proteins: Application to ps-ns Main Chain N-15-H-1 and Global Dynamics of the Rho GTPase Binding Domain of Plexin-B1
JOURNAL OF PHYSICAL CHEMISTRY B, 115:376-388, JAN 20 2011

An integrated computational methodology for interpreting NMR spin relaxation in proteins has been developed. It combines a two-body coupled-rotator stochastic model with a hydrodynamics-based approach for protein diffusion, together with molecular dynamics based calculations for the evaluation of the coupling potential of mean force. The method is applied to N-15 relaxation of N-H bonds in the Rho GTPase binding (RBD) domain of plexin-B1, which exhibits intricate internal mobility. Bond vector dynamics are characterized by a rhombic local ordering tensor, S, with principal values S0(2) and S-2(2), and an axial local diffusion tensor, D-2, with principal values D-2,D-parallel to and D-2,D-perpendicular to. For alpha-helices and beta-sheets we find that S0(2) similar to -0.5 (strong local ordering), -1.2 < S-2(2) < -0.8 (large S tensor anisotropy), D-2,D-perpendicular to similar to D-1 = 1.93 x 10(7) (D-1 is the global diffusion rate), and log(D-2 parallel to /D-1) similar to 4. For alpha-helices the z-axis of the local ordering frame is parallel to the C-alpha-C-alpha axis. For beta-sheets the z-axes of the S and D-2 tensors are parallel to the N-H bond. For loops and terminal chain segments the local ordering is generally weaker and more isotropic. On average, D-2,D-perpendicular to similar to D-1 also, but log(D-2,(parallel to)/ D-1) is on the order of 1-2. The tensor orientations are diversified. This study sets forth an integrated computational approach for treating NMR relaxation in proteins by combining stochastic modeling and molecular dynamics. The approach developed provides new insights by its application to a protein that experiences complex dynamics.

DOI:10.1021/jp108633v

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