Prediction of Protein Fold and Analysis of Protein Folding Procedure

蛋白质折叠的预测和蛋白质折叠过程的分析

• 批准号: 12680657
• 负责人: NAKAMURA Haruki
• 金额: $ 2.3万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12680657/
• 关键词: Simulation Computation; Molecular Dynamics; Peptide Conformation; Conformation Sampling; Quantum Chemistry; Disordered Structure; Tsallis Statistics; Multicanonical ensemble; β-ヘアピン; 水素結合

Our purpose is to predict the protein fold by computing the major free energy landscape of a protein molecule, since native conformations of proteins assume the conformations with low free energy values. In addition, the analysis of protein folding procedures are investigated.First, we chose two kinds of peptides with about 10 amino acids, and draw the free energy landscapes after enhanced conformational search. The resulted landscapes were consistent with the experiments of CD and NMR spectra.Further, we noticed that the landscapes were strongly dependent on the force field parameters, and so we made our effort on this problem. We developed a new algorithm to calibrate the free energy landscapes by the quantum chemical calculations, and we succeeded to calibrate several free energy landscapes, which were given by using different force fields, into the common landscape.In addition, we developed another method for the enhanced conformational search, by applying Tsallis statistics. When the parameter q in Tsallis statistics was treated as one of the variables for the motion of equation, the wide energy region can be covered by this new method for a simple peptide system composed of five amino acids.

我们的目的是通过计算蛋白质分子的主要自由能景观来预测蛋白质折叠，因为蛋白质的天然构象假定具有低自由能值的构象。此外，本文还对蛋白质折叠过程进行了分析。首先，我们选取了两种10个氨基酸左右的多肽，经过增强的构象搜索，绘制了它们的自由能图谱。结果表明，所得到的形貌与CD谱和NMR谱的实验结果相一致，并且发现形貌与力场参数有很强的依赖关系，因此我们对这一问题进行了研究。我们提出了一种新的基于量子化学计算的自由能景观校正算法，成功地将几种不同力场下的自由能景观校正到共同的景观中，另外，我们还提出了另一种基于Tsallis统计的增强构象搜索方法.当把Tsallis统计量中的参数q作为方程运动的变量之一时，对于一个由5个氨基酸组成的简单肽体系，这种新方法可以覆盖较宽的能量范围。

项目成果

Hitomi, Kenichi et al: "Role of two histidines in the (6-4) photolyase reaction"Journal of Biological Chemistry. Vol. 276, No. 13. 10103-10109 (2001)

Hitomi、Kenichi 等人：“两个组氨酸在 (6-4) 光裂合酶反应中的作用”生物化学杂志。

Higo, Junichi: "Energy landscape of a beta-hairpin peptide in explicit water studied by multicanonical molecular dynamics"Chemical Physics Letters. vol.377,No.1. 169-175 (2001)

Higo，Junichi：“通过多规范分子动力学研究的显式水中 β-发夹肽的能量景观”《化学物理快报》。

Higo, Junichi: "Energy landscape of a peptide consisting of alpha-helix, 3(10)-helix, beta-turn, beta-hairpin, and other disordered conformations"Protein Science. vol.10,No.6. 1160-1171 (2001)

Higo，Junichi：“由 α-螺旋、3(10)-螺旋、β-转角、β-发夹和其他无序构象组成的肽的能量景观”《蛋白质科学》。

Furukawa, Koji: "A role of the third complementarity-determining region in the affinity maturation of an antibody"Journal of Biological Chemistry. vol.276,No.29. 27622-27628 (2001)

Furukawa, Koji：“第三互补决定区在抗体亲和力成熟中的作用”生物化学杂志。

Higo,Junichi: "Energy landscape of a peptide consisting of α-helix, 3_<10>-helix, β-turn,β-hairpin, and other disordered conformations."Protein Science. (in press). (2001)

Higo，Junichi：“由α-螺旋、3_ 10 -螺旋、β-转角、β-发夹和其他无序构象组成的肽的能量景观。”蛋白质科学(2001年出版)。