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Tertiavy structure analysis of biomolecules based on X-ray and NMR data by multicawowical algorithm

基于 X 射线和 NMR 数据的生物分子三级结构分析，采用 multicawowical 算法

基本信息

批准号：
09480181
负责人：
OKAMOTO Yuko
金额：
$ 0.51万
依托单位：
OKAZAKI NATIONAL RESEARCH INSTITVTES
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

We have been advocating the uses of Monte Carlo simulated annealing and multi-canonical algorithms for the prediction of protein tertiary structures.We have been mainly trying the predictions from the first principles.However, it is the purpose of the present project to show that these methods can also be used for the structural refinement in X-ray and NMR experiments.In the first year of the project, we first introduced the RISM theory for accurate inclusion of solvent effects and combined RISM and simulated annealing method.As for multicanonical algorithms, it is non-trivial to obtain the probability factor for simulations.It is thus important to develop an efficient method that allows an easy determination of the weight factor.We have invented such a method based on Tsallis statistical mechanics and tested the effectiveness with a penta peptide, Met-enkephalin.In the second year of the project, we first developed a molecular dynamics version of the above new method that is based on Tsallis statistical mechanics.This is important, since structural refinements in X-ray and NMR experiments are usually based on molecular dynamics method.We further succeeded in the prediction of the tertiary structures of C-peptide of ribonuclease A by multicanonical simulations.We also predicted the tertiary structures of a bovine pancreatic trypsin inhibitor fragment by simulated annealing.It was found that these simulation results are in good agreement with those of X-ray and NMR experiments.

我们一直提倡使用蒙特卡洛模拟退火和多规范算法来预测蛋白质三级结构。我们主要尝试从第一原理进行预测。然而，本项目的目的是表明这些方法也可以用于X射线和核磁共振实验中的结构细化。在项目的第一年，我们首先引入了RISM理论来精确预测蛋白质的三级结构。包含溶剂效应并结合RISM和模拟退火方法。对于多规范算法，获得模拟的概率因子并非易事。因此，开发一种可以轻松确定权重因子的有效方法非常重要。我们发明了这种基于Tsallis统计力学的方法，并用五肽Met-脑啡肽测试了其有效性。在项目中，我们首先开发了基于 Tsallis 统计力学的上述新方法的分子动力学版本。这很重要，因为 X 射线和核磁共振实验中的结构精修通常基于分子动力学方法。我们进一步通过多规范模拟成功预测了核糖核酸酶 A C 肽的三级结构。我们还预测了牛的三级结构通过模拟退火法制备胰腺胰蛋白酶抑制剂片段。发现这些模拟结果与X射线和NMR实验的结果吻合得很好。