Advanced Computational Approaches to Biomolecular Modelling and Structure Determination

9318159 Schulten项目摘要高性能计算机，特别是大规模并行计算机，以及新兴的高容量研究网络将用于推进分子生物学和药理学中的建模和结构确定计算。为此，七名具有计算机科学、应用数学、分子生物学、药理学、化学和物理学专业知识的研究人员将联合收割机努力实现四个目标：（i）开发用于非常大、非常长和非常精确的分子动力学算法原型 （ii）将上述算法转移到广泛使用的结构生物学分子动力学程序（X-PLOR）中，并在该程序的框架内开发计算晶体学和溶液NMR光谱学的有效算法;（iii）使用NSF中心的计算测试平台，并将开发的程序应用于分子生物学和药理学的重大挑战问题，最初用于膜-蛋白质-水系统、药物的膜转运、DNA-蛋白质-水系统的结构测定和相互作用分子动力学，后来，对于大型超分子系统，如脊髓灰质炎病毒的外壳或肌肉纤维中的肌动蛋白-肌球蛋白链;（iv）开发一个图形用户界面，使本地图形工作站和NSF中心的远程大规模并行计算机之间能够方便地进行交互式分子建模，通过使用处于不同完成阶段的国家研究网络，开创了研究人员之间电话会议通信的常规使用，并建立了“计算生物学远程学院”，作为NSF中心和其他合格地点视频会议设施上的定期研讨会。

9318159 Schulten Project Summary High performance computers, in particular massively parallel computers, and the emergent, high-capacity research network will be employed to advance modelling and structure determination calculations in molecular biology and pharmacology. To this end, seven investigators with expertise in computer science, applied mathematics, molecular biology, pharmacology, chemistry, and physics will combine their efforts towards four goals: (i) to develop prototype molecular dynamics algorithms for very large, very long, and very accurate applications as well as to enhance the efficiency of such algorithms; (ii) to transfer the above algorithms to a widely used molecular dynamics program for structural biology (X-PLOR) and to develop, within the framework of this program, efficient algorithms for computational crystallography and solution NMR spectroscopy; (iii) to use the computational test beds of NSF centers and to apply the programs developed to grand challenge problems in molecular biology and pharmacology, initially for structure determination and interactive molecular dynamics of membrane-protein-water systems, of membrane transport of drugs, of DNA-protein-water systems and, later, for large supramolecular systems like the coat of poliovirus or actin- myosin strands in muscle fiber; (iv) to develop a graphic user interface which allows convenient interactive molecular modelling between local graphics workstations and remote massively parallel computers at NSF centers, to pioneer the routine use of teleconference communication between the investigators through use of the National Research Network in its various stages of completion, and to institute a "teleacademy for computational biology" as a regular seminar on the video conference facilities of the NSF centers and other qualified sites.