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、多肽和跨膜蛋白的膜上进行。这些类型的膜在生理上相关的液晶相中本质上是无序的，因此很难通过实验获得原子级结构数据。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性质与通过实验获得的性质进行比较，以便测试工作的有效性，并可能重新考虑先前对数据的解释。具体地说，这些模拟的许多分析都以提取有助于解释实验的双层性质为目标。这项研究的具体科学目标包括表征含有多不饱和脂肪酸的脂双层的材料性质，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CB2之间的相互作用，研究与RAFT形成相关的甾醇/脂混合物的详细分子结构，以及开发准确模拟膜系统的方法。为了执行这些项目，将使用升级和扩展的Beowulf式并行计算机进行精心规划的数百纳秒长的模拟。这项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向许多学生提供的研究实习，对本科生的教学产生重大影响。除了测试模拟方法、执行模拟以及分析/解释模拟结果外，学生还将在校园社区以及全国性和地区性科学会议上展示他们的结果。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，并将向未来的科学专业学生展示令人兴奋的机会。

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.