| Summary: | 碩士 === 國立臺灣師範大學 === 化學研究所 === 91 === Recent advance in computer simulation of peptide/protein at atomic level has allowed one to obtain folded structures in good agreement with experimental results for a number of peptides of about 20 amino acids, starting folding from a linear chain. In the this thesis, we use molecular dynamics simulation method to examined folding and stable structures of several peptides. First, we examine a 19mer, which was derived from a previously-studied, designed 20mer with a substitution of TSPd with VD at the site near the first turn. We carried out simulations of eight trajectories in total of about 120 ns. The present results showed that three strand anti-parallel -sheet is likely the most stable structure. In addition, the simulations showed that the second turn, which has a DPro, formed first, as expected. The role of Val4 in folding was discussed. Furthermore, we carried out calculation for D5DP mutant to examine effect of substitution of Asp5 at the first turn with a DPro in structure stability. Molecular interactions between strands and at turn segments were analyzed and discussed.
Second, we examined an N-terminus 17mer segment of ubiquitin -Like Protein,Rub1 (PDB code number 1BT0). It was seen that a hydrophobic cluster between strands formed first in simulations. In addition, we carried out simulations for six hydrophobic residues to examine effect of hydrophobic strength in structural stability. It was found that substitution at the thirteenth residue destabilizes the beta-hairpin structure most. Examination of the effect of the deletion of Gly10 in the stability of this peptide also gave that deletion of Gly, which removes G1 -bulge at turn, destabilized beta hairpin structure, consistent with the observed results in previous experimental studies for the same segment from another ubiquitin.
Third, we carried out simulations for a designed peptide, named BB model which has 12 residues. We focused on examinations of two effects in beta hairpin structure: mutations of four Thr residues and mutations of Asp, His, and Ser residues in this peptide. The simulation results showed that mutations of Asp, His, and Ser residues destabilized beta hairpin structure. Also, the two Thr residues near the C- and N-termini are more important in stabilizing hairpin structure than other two Thr residues near the turn.
Finally, we examine structural transition between two small -sheet proteins of 60 residues, cardiotoxin 3 and 5 (denoted CTX3 and CTX5), which differ four residues in their sequences. To lower down the transition energy barrier, we employed a locally enhanced sampling method in simulation. The simulations gave that mutation of CTX3 to CTX5 from CTX3 structure can get close to CTX5 structure but not reverse. The factors influencing the simulated results, including the presence of Pro30 and Pro33, steric hinderance, and other molecular interactions, were analyzed and discussed in this thesis.
|
|---|
