跨膜蛋白的计算模型和分子模拟研究

The transmembrane proteins are a series of proteins that span the entire biological membrane. The relationship between structure and function of transmembrane proteins is very important for understanding the molecular biology mechanism in cell, the computer-aided drug design and the structure prediction of membrane proteins. Since the systems of transmembrane proteins are very complex and they usually have large conformational changes, it is necessary to design the corresponding model according to their characters in molecular simulation. This project will explore the mechanism of substrate recognition and transport process for transmembrane protein by the study of computational and simulation approaches. According to the structure characters of transmembrane protein, the docking computational approach for transmembrane protein will be proposed on the basis of our previous studies. Combining coarse-grained elastic network model and molecular dynamics methods, the multi-scale simulations will be performed for the allosteric and transport process of transmembrane protein. Through the equilibrium and steered molecular dynamics simulations, we will explore the dynamics properties of the interaction process between transmembrane protein and substrate. This project will provide some useful exploration for the mechanism studies of substrate recognition and transport process of transmembrane protein.

跨膜蛋白是一类贯穿生物膜两端的蛋白质。跨膜蛋白的结构-功能关系对细胞中的分子生物学机理研究，计算机辅助药物设计和膜蛋白结构预测都具有重要的意义。跨膜蛋白体系比较复杂，并且往往具有大范围的构象变化，因此分子模拟需要考虑其特点有针对性的构建模型。本项目旨在通过计算模拟方法的研究，探索跨膜蛋白底物识别和转运过程的机制。针对跨膜蛋白的结构特征，结合课题组前期的研究基础，建立适合于跨膜蛋白的分子对接计算方法。综合粗粒化弹性网络模型和分子动力学对跨膜蛋白的变构和转运过程进行多尺度模拟。通过平衡态和拉伸分子动力学模拟，进一步探讨跨膜蛋白与底物相互作用过程中的动力学特性。该项目将为揭示跨膜蛋白底物识别和转运过程的机制提供有益的探索。

跨膜蛋白的结构-功能关系对细胞中的分子生物学机理研究，计算机辅助药物设计和膜蛋白结构预测都具有重要的意义。本项目采用分子动力学模型对跨膜蛋白水解酶Presenilin 1以及突触相关膜蛋白SV2系统进行了长时间平衡态动力学模拟, 考察了跨膜蛋白与底物分子、周围的磷脂分子以及水分子的相互作用。采用分子对接和分子动力学方法，研究了细胞膜表面补体受体CR2和植物光照PSII电子转运蛋白等跨膜蛋白与底物分子的识别和相互作用机制。建立了跨膜蛋白构象转变的粗粒化弹性网络模型，综合粗粒化模拟方法和非平衡态动力学研究了多个蛋白体系大尺度的构象转变过程。该项目为揭示跨膜蛋白底物识别和转运过程的机制提供有益的探索。在该基金的支持下，正式发表论文15篇，其中SCI收录10篇，另有多篇论文在投。其中，在《Biopolymers》杂志上发表的文章被作为当期封面论文。本工作还申请了软件著作权2项。