This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.We have performed 10 ns unrestrained MD simulations of the free and glycosylated STTAV peptide in explicit solvent. The MD data indicate that the free peptide STTAV is highly flexible, but that glycosylation of the S and T residues both stiffens and extends the backbone. These results are in complete agreement with a qualitative interpretation of the experimental data. Further, an examination of the unrestrained simulations shows good agreement with the experimentally determined structures. Despite the clear qualitative structural agreement, the 3JHH-values, derived initially from a Karplus-analysis of the each snapshot in the unrestrained MD simulation, were in poor overall agreement with the experimental values. To determine the extent to which this discrepancy originated in the MD conformations, restrained simulations were performed in which the MD data were forced to reproduce the experimental 3JHH-values. The use of 3JHH-restraints led to good agreement with the experimental 3JHH-values, and had generally very modest affects on the MD data. These results suggest that the individual states for the glycosidic-angles were correctly identified, but that the inaccuracies arose either from incorrect predictions of the populations of the conformational states or from errors in the empirical relationship. In order to establish the extent of any errors arising from the use of a Karplus-curve, we are developing methods to compute the QM-NMR J-couplings directly for each snapshot from the simulation.
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