RUI: Atomistic Simulations of Lipid Bilayer Membranes

分子动力学模拟将在含有各种磷脂以及小溶质、甾醇、肽和跨膜蛋白的膜上进行。这些类型的膜在生理学相关的液晶相中固有地是无序的，因此很难通过实验获得原子水平的结构数据。这些模拟将补充现有的实验数据，例如，将在模拟中观察到的特性和实验获得的特性之间进行比较，以检验工作的有效性，并可能重新考虑以前对数据的解释。具体而言，这些模拟的许多分析的目标是提取双层特性，以帮助解释实验。本研究的具体科学目的包括表征含有多不饱和脂肪酸的脂质双层的材料特性，描述多不饱和脂肪酸与跨膜蛋白视紫红质和外周大麻素受体CB 2之间的相互作用，研究与筏形成相关的甾醇/脂质混合物的详细分子结构，以及开发精确模拟膜系统的方法。为了实施这些项目，将使用一台贝奥武夫式的并行计算机进行精心策划的模拟，模拟时间长达数百纳秒，该计算机将升级和扩展。该研究计划将通过将分子建模技术从研究实验室转移到瓦巴什学院的化学课程，以及通过将在学年和夏季提供给众多学生的研究实习，对本科教学产生重大影响。除了测试模拟方法，进行模拟，分析/解释模拟结果，学生将展示他们的结果，以校园社区和国家和地区的科学会议。这些演讲将为他们作为科学研究人员的职业生涯做好准备，并将展示未来科学专业的令人兴奋的机会。

Molecular dynamics simulations will be carried out on membranes containing a variety of phospholipids, as well as small solutes, sterols, peptides, and trans-membrane proteins. These types of membranes are inherently disordered in the physiologically relevant liquid-crystalline phase, thus atomic-level structural data is difficult to obtain experimentally. These simulations will complement the existing body of experimental data, e.g., comparison will be made between properties observed in the simulation and those obtained experimentally in order to test the validity of the work and possibly to reconsider previous interpretations of the data. Specifically, many of the analyses for these simulations have as their goal the extraction of bilayer properties that aid in the interpretation of experiment. Specific scientific aims of this research include the characterization of material properties of lipid bilayers containing polyunsaturated fatty acids, a description of interactions between polyunsaturated fatty acids and the transmembrane proteins rhodopsin and peripheral cannabinoid receptor CB2, the investigation of detailed molecular structures in sterol/lipid mixtures relevant to raft formation, and the development of methods for the accurate simulation of membrane systems. To carry out these projects, carefully planned simulations, of hundreds of nanoseconds in length, will be carried out using a Beowulf-style parallel computer that will be upgraded and expanded. This research program will have significant impact on undergraduate instruction through the transfer of molecular modeling techniques from the research laboratory to the chemistry curriculum at Wabash College, as well as via the research internships that will be available to numerous students during the academic year and summer. In addition to testing simulation methods, carrying out simulations, and analyzing/interpreting simulation results, students will present their results to the campus community and at national and regional scientific meetings. These presentations will prepare them for careers as scientific researchers and will demonstrate exciting opportunities available to prospective science majors.