Development of a computer simulation system for particle-level molecular interactions

In this poster presentation, we will show our development of a particle-level simulation system targeted for analyses of biochemical reactions. Rate equations and molecular dynamics (MD) simulations are now widely used in the field of biochemistry and molecular biology. These two simulation techniques have also greatly contributed to application fields such as modeling of pathways and designing of drugs. When we use these techniques, however, we need to take into account that rate equations are suitable for describing macroscopic behavior or kinetics of some target molecules, while MD simulations are devoted to microscopic property of target proteins. Whereas these macroscopic and microscopic techniques have been matured, those for intermediate scales, i.e., length scales ranging from sub-μm to mm or time scales raging from sub-μs to s, seem to have needs for further sophistication since cellular processes within these scales often involve spatio-temporal properties that cannot be straightforwardly addressed by rate equations or MD simulations. In this respect, our particle-level approach is one of the promising candidates for simulation of biochemical reactions with such intermediate scales. A characteristic feature of our approach is that it explicitly takes account of spatial dynamics of molecules by expressing them as “particles”. Chemical reactions proceed through interactions of these particles in the space. When this simulation technique was applied to a mitogen-activated protein kinase (MAPK) cascade pathway model, we observed localization of activated MAPK molecules that give rise to significant decrease in overall ultrasensitivity.