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

我们一直提倡使用蒙特卡罗模拟退火和多规范算法来预测蛋白质三级结构。我们主要是在尝试从第一原理中做出预测。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，我们首先引入了精确包含溶剂效应的RISM理论，并将RISM与模拟退火方法相结合。对于多范式算法，其概率因子的获取具有重要的仿真意义。因此，重要的是开发一种有效的方法，使其能够容易地确定权重因子。我们基于Tsallis统计力学发明了这样一种方法，并用五肽Met-enkephalin测试了其有效性。在项目的第二年，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。这一点很重要，因为x射线和核磁共振实验中的结构改进通常基于分子动力学方法。我们进一步通过多谱模拟成功地预测了核糖核酸酶A c肽的三级结构。我们还通过模拟退火预测了牛胰蛋白酶抑制剂片段的三级结构。模拟结果与x射线和核磁共振实验结果吻合较好。

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.