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

The Salk Institute For Biological Studies, La Jolla CA

Investigators

Abstract

General Monte Carlo Simulation of Subcellular Biochemical Signaling, Phase II At 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