具兩對雙硫鍵胜鏈折疊之分子動力學模擬
Abstract
本論文是利用分子動力學模擬研究具有二組雙硫鍵的螺旋胜鍵的再折疊機制。在23條軌跡中，有20條軌跡折疊時間平均約10奈秒，其餘3條軌跡在100-200奈秒的模擬時間內並未能折疊至自然狀態。另外，不同起始軌跡23條軌跡中，有16條軌跡折疊至自然狀態，平均折疊時間約10奈秒，統計結果與之前結果有良好的一致性。在未折疊至自然態的8條軌跡中，觀察到其中5條軌跡形成中間態主因為非局部性、非自然氫鍵，而後更進一步地分析其餘3組軌跡，發現模擬時若有2組以上非自然氫鍵存在時，十分容易形成中間態構形，另外，我們也作了疏水聚集的測試，發現影響疏水作用力對折疊過程並無顯著影響。就目前所知，是首次以具有雙硫鍵的短胜鍵所進行的分子動力學模擬。
A molecular dynamics simulation of the folding of a short helical peptide with two disulfide bonds was carried out. In 23 trajectories, 20 trajectories folded with an average time of ~10 ns. The other 3 trajectories did not fold in 100-200 ns simulations. In an additional 23 simulations, 18 trajectories folded with an average folding time of ~10 ns, giving good results in confirming statistical certainty. In all 8 non-folded trajectories, a non-local, non-native hydrogen bond (H-bond) and an additional non-native H-bond were observed in 5 trajectories. A further analysis of the other 3 non-folded trajectories indicated that, at least, 2 non-native H-bonds are needed to trap this peptide in an intermediate. An examination of the hydrophobic clustering effect shows that this effect is not significant in the folding of this peptide. To our knowledge, this is the first folding simulation for a short helical peptide with disulfide bonds.
A molecular dynamics simulation of the folding of a short helical peptide with two disulfide bonds was carried out. In 23 trajectories, 20 trajectories folded with an average time of ~10 ns. The other 3 trajectories did not fold in 100-200 ns simulations. In an additional 23 simulations, 18 trajectories folded with an average folding time of ~10 ns, giving good results in confirming statistical certainty. In all 8 non-folded trajectories, a non-local, non-native hydrogen bond (H-bond) and an additional non-native H-bond were observed in 5 trajectories. A further analysis of the other 3 non-folded trajectories indicated that, at least, 2 non-native H-bonds are needed to trap this peptide in an intermediate. An examination of the hydrophobic clustering effect shows that this effect is not significant in the folding of this peptide. To our knowledge, this is the first folding simulation for a short helical peptide with disulfide bonds.
Description
Keywords
雙硫鍵, 胜鏈, 分子動力學