G蛋白偶联受体结构并行化预测的研究
发布时间：2019-01-16 06:43
【摘要】：G蛋白偶联受体(GPCR)的结构特征及其在信号传导中的重要作用，决定了其可以作为重要的药物靶标， GPCR在制药领域中占有极其重要的地位。由于生化实验方法很难得到其三维结构，所以通过计算机方法预测其结构具有重大意义。本文在GPCR结构预测中引入并行技术，研究GPCR骨架和侧链结构预测问题。 考虑到GPCR跨膜螺旋区域（TMH）同源性较高，而连接TMH的loop区域同源性很低，本文基于当前主流的GPCR蛋白质结构预测方法提出了一种并行化的GPCR骨架结构预测方法pGPCR。该方法在构建TMH区域时采用基于模板的方法，在构建loop时采用从头预测的方法。将并行技术引入到loop预测中，在loop并行折叠过程中考虑到loop之间的相互影响，使得整个预测过程更加符合自然的折叠过程。用pGPCR对最新的权威测试中两个案例的三维结构进行了预测，从整体结果集的质量上来看，本文方法不仅在TMH部分能够取得好的结果，，而且结果集中ECL2部分质量也较高。实验结果还表明，对于具有β折叠这种loop之间存在强烈相互影响的loop区域，本文预测的结果也更加接近天然结构。 在GPCR侧链预测研究方面，本文首先改进了GPCR侧链搜索空间生成方法，考虑了侧链之间的相互影响，提出了一种基于四层推理模型的旋转异构体库构造方法，并对3种GPCR蛋白质进行了侧链预测实验，验证了本文生成的旋转异构体库质量接近于流行的方法。本文又采用了新的侧链预测并行搜索方法，在共享信息素矩阵的基础上，并行化多个蚁群，并多样化各个蚁群的能量函数和参数。然后用该方法对pGPCR生成的最好的5个结果进行了侧链预测，结果表明本文方法具有一定的竞争力。
[Abstract]:The structural characteristics of G-protein-coupled receptor (GPCR) and its important role in signal transduction determine that it can be used as an important drug target, and GPCR plays an extremely important role in pharmaceutical field. Because it is difficult to obtain the three-dimensional structure by biochemical experiment method, it is of great significance to predict its structure by computer method. In this paper, parallel technique is introduced into GPCR structure prediction to study the prediction of GPCR skeleton and side chain structure. Considering the high homology of (TMH) in transmembrane helical region of GPCR and the low homology of loop region connected with TMH, this paper proposes a parallel GPCR skeleton structure prediction method pGPCR. based on the current mainstream GPCR protein structure prediction method. In this method, template based method is used to construct TMH region, and ab initio prediction method is used to construct loop. The parallel technique is introduced into loop prediction, and the interaction between loop is considered in the process of loop parallel folding, which makes the whole prediction process more consistent with the natural folding process. PGPCR is used to predict the 3D structure of the two cases in the latest authoritative test. From the quality of the whole result set, this method can not only obtain good results in the TMH part, but also the higher quality of the ECL2 part in the result set. The experimental results also show that the predicted results of this paper are closer to the natural structure for the loop region with strong interaction between loop and 尾 -fold. In the aspect of GPCR side chain prediction, this paper first improves the GPCR side chain search space generation method, considers the interaction between the side chains, and proposes a new method to construct the rotating isomer library based on the four-layer reasoning model. The side chain prediction experiments of three kinds of GPCR proteins were carried out, and the results showed that the quality of the rotating isomer pool was close to that of the popular method. Based on the shared pheromone matrix, a new side-chain predictive parallel search method is proposed to parallelize multiple ant colonies and diversify the energy functions and parameters of each ant colony. Then the best five results generated by pGPCR are predicted by this method, and the results show that the proposed method is competitive to some extent.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R341
本文编号：2409559
[Abstract]:The structural characteristics of G-protein-coupled receptor (GPCR) and its important role in signal transduction determine that it can be used as an important drug target, and GPCR plays an extremely important role in pharmaceutical field. Because it is difficult to obtain the three-dimensional structure by biochemical experiment method, it is of great significance to predict its structure by computer method. In this paper, parallel technique is introduced into GPCR structure prediction to study the prediction of GPCR skeleton and side chain structure. Considering the high homology of (TMH) in transmembrane helical region of GPCR and the low homology of loop region connected with TMH, this paper proposes a parallel GPCR skeleton structure prediction method pGPCR. based on the current mainstream GPCR protein structure prediction method. In this method, template based method is used to construct TMH region, and ab initio prediction method is used to construct loop. The parallel technique is introduced into loop prediction, and the interaction between loop is considered in the process of loop parallel folding, which makes the whole prediction process more consistent with the natural folding process. PGPCR is used to predict the 3D structure of the two cases in the latest authoritative test. From the quality of the whole result set, this method can not only obtain good results in the TMH part, but also the higher quality of the ECL2 part in the result set. The experimental results also show that the predicted results of this paper are closer to the natural structure for the loop region with strong interaction between loop and 尾 -fold. In the aspect of GPCR side chain prediction, this paper first improves the GPCR side chain search space generation method, considers the interaction between the side chains, and proposes a new method to construct the rotating isomer library based on the four-layer reasoning model. The side chain prediction experiments of three kinds of GPCR proteins were carried out, and the results showed that the quality of the rotating isomer pool was close to that of the popular method. Based on the shared pheromone matrix, a new side-chain predictive parallel search method is proposed to parallelize multiple ant colonies and diversify the energy functions and parameters of each ant colony. Then the best five results generated by pGPCR are predicted by this method, and the results show that the proposed method is competitive to some extent.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R341
【参考文献】
相关期刊论文 前2条
1 缪大俊;吕强;黄旭;;一种基于四层推理模型的旋转异构体库构造方法[J];苏州大学学报(自然科学版);2011年04期
2 缪大俊;吕强;吴宏杰;陈沙沙;;一种并行化的GPCR结构预测方法[J];苏州大学学报(自然科学版);2012年03期
本文编号：2409559
本文链接：https://www.wllwen.com/xiyixuelunwen/2409559.html
最近更新
教材专著
