Models of macromolecular crowding effects and the need for quantitative comparisons with experiment

Abstract

In recent years significant effort has been devoted to exploring the potential effects of macromolecular crowding on protein folding and association phenomena. Theoretical calculations and molecular simulations have, in particular, been exploited to describe aspects of protein behavior in crowded and confined conditions and many aspects of the simulated behavior have reflected, at least at a qualitative level, the behavior observed in experiments. One major and immediate challenge for the theorists is to now produce models capable of making quantitatively accurate predictions of in vitro behavior. A second challenge is to derive models that explain results obtained from experiments performed in vivo, the results of which appear to call into question the assumed dominance of excluded-volume effects in vivo.

Figure 1. Do macromolecular crowding agents mimic intracellular environments ?

At left is shown a solution of an idealized, spherical crowding agent of the type typically used in calculations and molecular simulations (figure prepared with VMD [83]). At right is a representation of the type of system that such crowding agents are usually intended to mimic: an atomically detailed model of the cytoplasm of Escherichia coli (McGuffee & Elcock; unpublished). Are the differences between the two images more important than the similarities?