具多帶電殘基胜?鏈折疊之分子動力學模擬

魏忠誠

指導教授 ： 孫英傑

國立臺灣師範大學/理學院/化學系/碩士(2004年)

摘要

無資料

關鍵字

分子動力學模擬

並列摘要

Abstract
A molecular dynamics simulation of the folding of conantokin-T (con-T), a short helical peptide with 5 helical turns of 21 amino acids with10 charged residues, was carried out to examine folding pathways for this peptide and to predict the folding rate. In the 18 run 300 K trajectories, 16 trajectories folded, with an averaged folding time of ~50 ns. 2 trajectories did not fold in up to 200 ns simulation. An analysis of the trajectories showed that, at the beginning of a few ns, helix formation started from residues 5-9 with assistance of a hydrophobic clustering involving Tyr5, Met8, and Leu9. The peptide formed a U-shape mainly due to charge-charge interactions between charged residues at the N- and C- terminus segments. In the next ~10 ns, several non-native charge-charge interactions were broken and non-native Gla10-Lys18 (this denotes a salt bridge between Gla10 and Lys18) and/or Gla10-Lys19 interactions appeared more frequently in this folding step and the peptide became a fishhook J-shape. From this structure, the peptide folded to the folded state in 7 of all 16 folded trajectories in ~15 ns. Alternatively, in ~30 ns, they can make the con-T in a L-shape with 4 helical turns and a kink at the Arg13 and Gla14 segment in 9 folded trajectories. Con-T in the L-shape then required another ~15 ns to fold into the folded state. In addition, in overall folding times, the former 7 trajectories folded faster with the total folding times all shorter than 45 ns while the latter 9 trajectories folded at a time longer than 45 ns, resulting in an average folding time of ~50 ns. Two major folding intermediates found in 2 non-folded trajectories are stabilized by charge clusters of 5 and 6 charged residues, respectively. The predicted folding time of ~50 ns, which is shorter than the folding time of 82 ns for an alanine-based peptide of the same length, suggests that the energy barrier of folding for this type of peptide with many charged residues is smaller than alanine-based helical peptides slightly.