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，阶段1在分子水平上，细胞同时具有高度组织性和非组织性。细胞的许多蛋白质构成块形成高度有组织的结构，用于各种目的，如细胞之间的通信和保持细胞在一起。另一方面，当小信号分子被释放时，它们可以以一种看似无组织的方式在随机方向上弹跳，直到它们在另一个分子（如蛋白质或DNA片段）上找到一个结合位点。这两种形式的组织和破坏是一种叫做MCell的新计算机程序的核心。该程序跟踪单个分子在一个真实的三维世界中弹跳的过程，这个三维世界中充满了大型蛋白质和其他高度组织的结构，这些结构精确地模仿了细胞的形状和内容。这笔拨款的目的是扩大MCell的能力，以模拟细胞内发生的分子过程和细胞之间发生的交流。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. Stiles）和康奈尔大学（E.E. Salpeter）共同进行。目前，全世界有超过21个实验室正在使用MCell来研究神经-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。赠款还将提供图形用户界面的开发，这将使使用程序更容易和更快，并提供广泛的文档，使新用户更容易访问MCell。MCell最重要的新特征之一是它能够模拟真实细胞的复杂三维结构，这些结构可能非常复杂且难以可视化。一种新的图形工具，用于重建，编辑和可视化三维细胞结构，仅用电子显微镜观察到的水平将被纳入下一代MCell。这也将使MCell用户有可能将他们重建的模型存入一个基于网络的档案，这将促进研究人员之间模型的积累和自由交换。到2003年，MCell用户将增加数百人。mccell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电脑，再到大型超级计算机。这笔资金支持的对MCell的补充将极大地扩展可以使用MCell进行检查的问题范围，从而使在计算机中模拟整个细胞功能的那一天更加接近。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，既可以帮助开始科学教育的学生可视化细胞的特性，也可以让高级学生使用该程序作为一种手段，在分子水平上探索复杂的、有时违反直觉的世界。有关MCell的更多信息和计算机生成的细胞在分子水平上的图像，请访问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