Tertiary structure prediction of peptides by Monte Carlo simulated annealing and its experimental verification

蒙特卡罗模拟退火肽三级结构预测及其实验验证

• 批准号: 04680164
• 负责人: NAKAZAWA Takashi
• 金额: $ 1.28万
• 依托单位: NARA WOMEN'S UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04680164/
• 关键词: Monte Carlo; Simulated anneling; Energy minimization; BPTI; Tertiary structure; Structural prediction; NMR; Protein folding; タンパク質のfolding; タンパク質の立体構造予測; β-シート構造; タンパク質の折りたたみ

A tertiary structure of the peptide fragment corresponding to residues 16-36 of bovine pancreatic trypsin inhibitor (BPTI) is predicted nsing Monte Carlo simulated annealing. The simulation starts with randomly chosen initial conformations and is performed without imposing experimental constraints. Out of 20 siumulation trials, seven conformations show a sheet-like structure-two strands connected by a turn-although this sheet-like structure is not as rigid as that observed in native BPTI.These conformations are mostly looped and exhibit a native-like right-handed twist. However, the lowest-energy conformation does not resemble exactly the native structure. This indicates that the rigid beta-sheet conformation of native BPTI merely corresponds to a local minimum of the energy function if the fragment with residues 16-36 is isolated from the native protein. Two-dimensional NMR analyzes of BPTI (16-36) in dimethylsulfoxide solution also denied the existence of rigid beta-sheet conformation with the proper hydrogen bonds. A statistical analysis of all 20 final conformations suggests that the tendency for the peptide segments to from extended beta-strands is strong for those with residues 18-24, and moderate for those with residues 30-35. The segment of residues 25-29 does not tend to form any definite structure. In native BPTI,the former segments are involved in the beta-sheet and the latter in the turn. Based on this analysis, a novel folding scenario is proposed.The same algorithm successfully predicted alpha-helical structure of parathynoid hormore fragment (34 amino acids). Therefore, it should be emphasized that the present method was capable of predicting tertiary structure of peptides depending only on their amino acid sequence data as inputs.

用MonteCarlo模拟退火法预测了牛胰胰蛋白酶抑制剂（BPTI）16-36位残基的三级结构。模拟从随机选择的初始构象开始，并且在不施加实验约束的情况下进行。在20个模拟实验中，有7个构象呈现片状结构，即两条链之间由一个转角连接，但这种片状结构不如天然BPTI中观察到的那样刚性，这些构象大部分是环状的，并表现出天然的右旋扭曲。然而，最低能量构象并不完全类似于天然结构。这表明，如果从天然蛋白质中分离具有残基16-36的片段，则天然BPTI的刚性β-折叠构象仅对应于能量函数的局部最小值。BPTI（16-36）在二甲基亚砜溶液中的二维NMR分析也否认了具有适当氢键的刚性β-折叠构象的存在。对所有20种最终构象的统计分析表明，具有残基18-24的肽段形成延伸的β链的趋势很强，而具有残基30-35的肽段形成延伸的β链的趋势中等。残基25-29的片段不倾向于形成任何确定的结构。在天然BPTI中，前一个片段参与β折叠，后一个片段参与转角。在此基础上，提出了一种新的折叠方案，同样的算法成功预测了甲状旁腺激素片段（34个氨基酸）的α-螺旋结构。因此，应该强调的是，本方法能够仅依赖于作为输入的肽的氨基酸序列数据来预测肽的三级结构。

项目成果

Takashi Nakazawa, Hikaru Kawai, Yuko Okamoto, and Masataka, Fukugita: ""beta-Sheet folding fragment (16-36) of bovine pancreatic trypsin inhibitor as predicted by Monte Carlo simulated annealing"" Protein Engineering. vol.5, no.6. 495-503 (1992)

Takashi Nakazawa、Hikaru Kawai、Yuko Okamoto 和 Masataka, Fukugita：“蒙特卡罗模拟退火预测的牛胰腺胰蛋白酶抑制剂的 β-Sheet 折叠片段 (16-36)”“蛋白质工程”。

Takashi Nakazawa: "β-Sheet folding of fragment(16-36)of bovine pancreatic trypsin inhibitor as predicted by Monte Carlo simulated annealing" Protein Engineering. 5. 495-503 (1992)

Takashi Nakazawa：“通过蒙特卡罗模拟退火预测牛胰腺胰蛋白酶抑制剂片段 (16-36) 的 β 片折叠”《蛋白质工程》5. 495-503 (1992)。

Takashi Nakazawa: "β-Sheel folding of fragment(16-36)of bovine pancreatic trypsin inhibitor as predicted by Monte Carlo simulated annealing" Protein Engineering. 5. 495-503 (1992)

Takashi Nakazawa：“通过蒙特卡罗模拟退火预测牛胰蛋白酶抑制剂片段 (16-36) 的 β-Sheel 折叠”Protein Engineering 5. 495-503 (1992)。

Yuko Okamoto: "α-Helix structure of parathyroid hormone fragment(1-34)predicted by Monte Carlo simulated annealing" International Journal of Peptide & Protein Research. 42. 300-303 (1993)

Yuko Okamoto：“通过蒙特卡罗模拟退火预测甲状旁腺激素片段 (1-34) 的 α-螺旋结构”国际肽与蛋白质研究杂志 42. 300-303 (1993)。

中沢 隆: "β-Sheet Folding of Fragment (16-36) of Bovine Pancreatic Trypsin Inhibitor as Predicted by Monte Carlo Simulated Annealing" Protein Engineering. 5. 495-503 (1992)

Takashi Nakazawa：“蒙特卡罗模拟退火预测的牛胰蛋白酶抑制剂片段 (16-36) 的 β 片折叠”《蛋白质工程》5. 495-503 (1992)。