Advanced Computational Approaches to Biomolecular Modelling and Structure Determination

高性能计算机，特别是大规模并行计算机，以及新兴的、高容量的研究网络将被用于推进分子生物学和药理学的建模和结构确定计算。为此，七位具有计算机科学、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共同努力实现四个目标：(i)为非常大、非常长、非常精确的应用开发原型分子动力学算法，并提高这些算法的效率；（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用于计算晶体学和溶液核磁共振光谱的有效算法；（iii）使用国家科学基金会中心的计算试验台，并将开发的程序应用于分子生物学和药理学中的重大挑战问题，最初用于膜-蛋白质-水系统，药物的膜运输，dna -蛋白质-水系统的结构确定和相互作用分子动力学，后来用于大型超分子系统，如脊髓灰质炎病毒外壳或肌动蛋白-肌球蛋白链在肌肉纤维中；（iv）开发一个图形用户界面，使本地图形工作站和美国国家科学基金会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，并通过使用国家研究网络在其完成的各个阶段在研究人员之间常规使用电话会议通信；并建立一个“计算生物学远程学院”，作为在国家科学基金会中心和其他合格地点的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.