Coarse-grained molecular dynamics simulations of the bacterial cell wall

Abstract

Understanding mechanisms of bacterial sacculus growth is challenging due to the time and length scales involved. Enzymes three orders of magnitude smaller than the sacculus somehow coordinate and regulate their processes to double the length of the sacculus while preserving its shape and integrity, all over a period of tens of minutes to hours. Decades of effort using techniques ranging from biochemical analysis to microscopy have produced vast amounts of data on the structural and chemical properties of the cell wall, remodeling enzymes and regulatory proteins. The overall mechanism of cell wall synthesis, however, remains elusive. To approach this problem differently, we have developed a coarse-grained simulation method in which, for the first time to our knowledge, the activities of individual enzymes involved are modeled explicitly. We have already used this method to explore many potential molecular mechanisms governing cell wall synthesis, and anticipate applying the same method to other, related questions of bacterial morphogenesis. In this chapter, we present the details of our method, from coarse-graining the cell wall and modeling enzymatic activities to characterizing shape and visualizing sacculus growth.