General Monte Carlo Computer Simulation of Subcellular Biochemical Signaling: Phase II

亚细胞生化信号的一般蒙特卡罗模拟，在分子水平上，细胞是高度有序的，同时也是无序的。许多细胞的蛋白质组成块形成高度有序的结构，用于各种目的，如细胞之间的通信和将细胞保持在一起。另一方面，当小的信号分子被释放时，它们可能会以一种看似杂乱无章的方式在随机方向上反弹，直到它们在另一种分子上找到一个结合位置，比如蛋白质或DNA片段。这两种组织形式和混乱形式是一种名为Mcell的新计算机程序的核心。这个程序跟踪单个分子在一个现实的三维世界中弹跳，这个世界充满了大型蛋白质和其他高度组织的结构，这些结构准确地模拟了细胞的形状和内容。这笔赠款的目的是扩大MCell模拟细胞内发生的分子过程和细胞之间发生的通信的能力。这项研究将由索尔克研究所(T.J.Sejnowski和T.M.Bartol)、卡内基梅隆大学(J.R.斯泰尔斯)和康奈尔大学(E.E.Salpeter)联合进行。目前，全球超过21个实验室正在使用Mcell研究神经-肌肉突触和大脑中各种突触的突触传递，以及肝脏等其他器官细胞的生化过程。这笔赠款还将用于开发图形用户界面，这将使该程序的使用变得更容易和更快，并提供大量文档，使Mcell更容易为新用户所用。Mcell最重要的新功能之一是它能够模拟真实细胞的复杂三维结构，这可能是高度复杂和难以可视化的。一种新的图形工具，用于在仅用电子显微镜观察的水平上重建、编辑和可视化三维细胞结构，将被整合到下一代Mcell中。这也将使Mcell用户能够将他们重建的模型存入基于网络的档案中，这将促进研究人员之间模型的积累和自由交流。到2003年，将有数百名额外的Mcell用户。Mcell模拟可以在各种各样的平台上运行，从手持计算器到标准个人计算机，再到大型超级计算机。这项拨款将支持对Mcell的增加，这将极大地扩大可以使用MCell检查的问题的范围，使模拟计算机中整个单元的功能的日子更近了。随着图形用户界面的增加，未来开发阶段的一个主要目标将是使Mcell成为一种教学工具，既适用于刚开始科学教育的学生，帮助他们可视化细胞的属性，也适用于高级学生，他们可以使用该程序作为一种手段，在分子水平上探索复杂的、有时与直觉相反的世界。有关Mcell和计算机生成的分子水平上的细胞图像的更多信息，请参见http://www.mcell.cnl.salk.edu或http://www.mcell.psc

General Monte Carlo Simulation of Subcellular Biochemical Signaling, Phase IIAt the molecular level, cells are highly organized and disorganized at the same time. Many of the protein building blocks of cells form highly organized structures used for a variety of purposes, such as communication between cells and holding cells together. On the other hand, when small signaling molecules are released they can bounce around in random directions in a seemingly disorganized way, until they find a binding site on another molecule like a protein or section of DNA. These two forms of organization and disorganization are at the heart of a new computer program called MCell. This program follows individual molecules as they bounce around a realistic three-dimensional world populated with large proteins and other highly organized structures that accurately mimic the shape and contents of a cell. The purpose of this grant is to expand MCell's ability to simulate the molecular processes that take place inside cells and the communication that occurs between cells. The research will be carried out jointly between The Salk Institute (T.J. Sejnowski and T.M. Bartol), Carnegie Mellon University (J.R. Stiles), and Cornell University (E.E. Salpeter). Over 21 laboratories around the world are currently using MCell to study synaptic transmission at the nerve-muscle synapse and a wide variety of synapses in the brain, as well as biochemical processes in cells of other organs such as the liver. The grant will also provide for the development of a graphical user interface, which will make it easier and faster to use the program, and extensive documentation to make MCell more accessible to new users. One of the most important new features of MCell is its ability to model the complex three-dimensional structure of real cells, which can be highly convoluted and difficult to visualize. A new graphical tool for reconstructing, editing, and visualizing three-dimensional cellular structures at the level observed only with electron microscopes will be incorporated into the next generation of MCell. This will also make it possible for MCell users to deposit their reconstructed models into a web-based archive, which will promote the accumulation and free exchange of models among researchers. There will be several hundred additional MCell users by 2003. MCell simulations may be run on a wide range of platforms, from hand-held calculators, to standard personal computers, to large-scale supercomputers. The additions to MCell that will be supported on this grant will greatly expand the range of problems that can be examined using MCell, bringing closer the day when it will be possible to simulate the functions of an entire cell in a computer. With the addition of the graphical user interface, a major aim of a future phase of development will be to make MCell available as a teaching tool both for students who are beginning their science education, to help them visualize the properties of cells, and for advanced students, who can use the program as a means to explore the complex and sometimes counterintuitive world at the molecular level. For more information about MCell and computer-generated images of what cells might look like at the molecular level, see http://www.mcell.cnl.salk.edu or http://www.mcell.psc