Motion-Planning Based Techniques for Modeling & Simulating Molecular Motions

基于运动规划的建模技术

• 批准号: 0830753
• 负责人: Nancy Amato
• 金额: $ 37万
• 依托单位: Texas A&M Engineering Experiment Station
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2014-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0830753&HistoricalAwards=false
• 关键词: Motion; Planning; Based; Techniques; Modeling

NUMBER: 0830753INSTITUTION: Texas Engineering Experiment StationPI: Amato, Nancy & Rauchwerger, LawrenceTITLE: Motion-Planning Based Techniques for Modeling & Simulating Molecular MotionsMolecular motions play an essential role in many biochemical processes. Since it is difficult to experimentally observe molecular motions, computational methods for studying such issues are essential. This research investigates a novel computational method for studying molecular motions that the investigators have developed and validated against experimental data in preliminary work. The research has the potential to provide insight into a number of important questions related to protein folding, stability, and solubility. For example, protein misfolding and aggregation is associated with devastating neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, prion diseases, and related diseases. In addition to publications, results generated by the research are shared with the community in a publicly available database of molecular motions. The protein folding server also allows scientists to submit their own proteins which will be analyzed for them: http://parasol.tamu.edu/foldingserver/.The new computational method invested in this research represents a trade-off between methods such as molecular dynamics and Monte Carlo simulations that provide detailed individual folding trajectories and techniques such as statistical mechanical methods that provide global folding landscape statistics. This method builds a graph (roadmap) corresponding to an approximate map of the molecule's energy landscape that encodes many (typically thousands) folding pathways. Though the individual pathways produced are not as detailed as trajectories generated from a molecular dynamics simulation, they can be used to study properties such as secondary structure formation order and folding kinetics. The major research goals of this project include the development of new and/or improved metrics and analysis techniques for conformations and roadmaps that can be applied in protein stability and kinetics studies and the development of strategies for employing high-performance computing to increase the size and complexity of the systems that can be studied. The investigators validate and apply these new techniques to folding core identification, amyloid formation, kinetics studies, and comparative analysis of proteins.

编号：0830753机构：德克萨斯工程实验站PI：Amato、Nancy 和 Rauchwerger、Lawrence 标题：基于运动规划的分子运动建模和模拟技术分子运动在许多生化过程中发挥着重要作用。 由于很难通过实验观察分子运动，因此研究此类问题的计算方法至关重要。 这项研究探讨了一种研究分子运动的新颖计算方法，研究人员在前期工作中开发并根据实验数据进行了验证。 该研究有可能深入了解与蛋白质折叠、稳定性和溶解度相关的许多重要问题。 例如，蛋白质错误折叠和聚集与毁灭性的神经退行性疾病有关，例如阿尔茨海默病、帕金森病、朊病毒病和相关疾病。 除了出版物之外，研究产生的结果还通过公开的分子运动数据库与社区共享。 蛋白质折叠服务器还允许科学家提交自己的蛋白质，这些蛋白质将被分析：http://parasol.tamu.edu/foldingserver/。这项研究中投入的新计算方法代表了分子等方法之间的权衡动力学和蒙特卡罗模拟提供详细的个体折叠轨迹和技术，例如提供全局折叠景观统计的统计机械方法。 该方法构建了一个与分子能量景观的近似图相对应的图（路线图），该图编码了许多（通常是数千个）折叠路径。 尽管产生的各个路径不如分子动力学模拟生成的轨迹那么详细，但它们可用于研究二级结构形成顺序和折叠动力学等特性。 该项目的主要研究目标包括开发新的和/或改进的构象和路线图度量和分析技术，可应用于蛋白质稳定性和动力学研究，以及开发采用高性能计算来增加尺寸和结构的策略。可以研究的系统的复杂性。 研究人员验证了这些新技术并将其应用于折叠核心识别、淀粉样蛋白形成、动力学研究和蛋白质比较分析。