Comparisons of three-dimensional structures of proteins using hierarchical models and regularization for between-protein variations

使用分层模型和蛋白质间变异正则化比较蛋白质的三维结构

• 批准号: 22500275
• 负责人: AMISAKI Takashi
• 金额: $ 2.66万
• 依托单位: Tottori University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22500275/
• 关键词: 統計数学; 生体分子; 蛋白質; 生体生命情報学

A method for comparing protein structures was developed. We consider a collection of three-dimensional coordinates of multiple proteins in which each protein has multiple conformations. The method exploits this protein-conformation hierarchy, and is based on the mixed-effects models on between- and within-protein variability. The estimation procedure is that of the EM-algorithm, in which the individual deviations of proteins are estimated and restricted using maximum-a-posteriori estimatorsand L1-regularization. At each iteration of the algorithm, the superposition of conformations can be made using a usual singular-value-decomposition but for specializedcovariance matrices. The results of numerical tests indicate that the method can be effective for characterizing the structures of multiple proteins simultaneously.

开发了一种比较蛋白质结构的方法。我们考虑多个蛋白质的三维坐标的集合，其中每个蛋白质具有多种构象。该方法利用了这种蛋白质构象层次结构，并基于蛋白质间和蛋白质内变异性的混合效应模型。估计过程是 EM 算法的过程，其中使用最大后验估计器和 L1 正则化来估计和限制蛋白质的个体偏差。在算法的每次迭代中，可以使用通常的奇异值分解来进行构象的叠加，但对于专门的协方差矩阵。数值试验结果表明该方法可有效同时表征多种蛋白质的结构。

项目成果

Steric and Allosteric Effects of Fatty Acids on the Binding of Warfarin to Human Serum Albumin Revealed by Molecular Dynamics and Free Energy Calculations

• DOI: 10.1248/cpb.59.860
• 发表时间: 2011-07-01
• 期刊: CHEMICAL & PHARMACEUTICAL BULLETIN
• 影响因子: 1.7
• 作者: Fujiwara, Shin-ichi;Amisaki, Takashi
• 通讯作者: Amisaki, Takashi