| Summary: | 碩士 === 國立臺灣師範大學 === 化學研究所 === 90 === Ubiquitin is a protein of abundant experimental data for stability and folding/unfolding studies. It consists of five beta + one helix strands. The N-terminal segment of Res1-17 is one of the few cases where a short peptide can populate the monomeric beta hairpin conformation in aqueous solution. In the present study, we carried out molecular dynamics (MD) simulation to examine conformational stability for this peptide and its mutants using GB/SA solvation model. Delection of glycine at turn segment of this ubiquitin peptide destabilizes the β-hairpin as observed in experiment. In addition, we replaced the turn segment of TLTGK with several turn-location-favored segments, including NPDGT, NG, AG, and, GD, in this peptide. The simulation results shows that the TLTGK is more stable than NPDGT segment for this beta hairpin peptide, consistent with experimental observation. Other turn mutations also showed less stability compared with the original TLTGK segment in this ubiquitin peptide.
In addition, we carried out a folding MD simulation of a peptide of NG turn and non-polar residues on the strands at 300 K. Starting from unfolded structure, the trajectory showed that the beta hairpin formed at 50 ps and maintains up to 1.6 ns. The fast folding is consistent with experimental observation. With a mutation of GD segment with NG segment, the beta hairpin structure significantly destablized. The backbone dihedral angles, orientation of side chains and formation of hydrogen bonds will be reported and analyzed.
Finally, we examined the conformational transition between two cardiotoxins, CTX2 and CTX3, which differ six residues in their sequence. The simulation results show that the mutation from CTX3 to CTX2 can get close to CTX2 structure but not reverse. With implement of a locally enhanced sampling (LES) method, the conformational transition is enhanced to some extend. The factors influencing the simulated results, including presence of prolines, steric effect etc., will be
analyzed and discussed.
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