LYSINE SIDE-CHAIN DYNAMICS DERIVED FROM C-13-MULTIPLET NMR RELAXATIONSTUDIES ON DIPEPTIDES AND TRIPEPTIDES

C-13 NMR relaxation data have been used to determine dipolar auto- and cross-correlation times for the di- and tripeptides GK, KG and GKG, p rimarily to analyze lysine side-chain motional dynamics. In general, c orrelation times are largest for backbone positions and decrease on go ing through the lysine side chain, consistent with the idea of increas ed mobility at C-delta and C-epsilon methylenes. Correlation times, ho wever, vary with the peptide ionization state. In the zwitterionic sta te of GK, for example, both auto-and cross-correlation times are at th eir maximum values, indicating reduced internal motions probably resul ting from intramolecular electrostatic interactions. Modifying the cha rge state increases motional fluctuations. Activation energies determi ned from the temperature dependence of CH rotational autocorrelation t imes at neutral pH are approximately equal for glycine and lysine C-al pha and lysine C-beta and C-gamma positions (4.1 +/- 0.2 to 4.5 +/- 0. 2 kcal/mol) and tend to decrease slightly for lysine C-delta and C-eps ilon (3.8 +/- 0.2 to 4.3 +/- 0.2 kcal/mol). The sign of lysine side-ch ain cross-correlations could not be explained by using any available r otational model, including one parameterized for multiple internally r estricted rotations and anisotropic overall tumbling. Molecular and st ochastic dynamics calculations were performed to obtain insight into c orrelated internal rotations and coupled overall tumbling and internal motions. Relatively strong correlations were found for i,i + 1 backbo ne and lysine side-chain internal bond rotations. Stochastic dynamics calculations were more successful at explaining experimentally observe d correlation times. In the fully charged state, a preferred conformat ion was detected with an all-trans lysine side chain.