Protein folding requires crowd control in a simulated cell

Film presented at ISMB 2010 to illustrate my recent paper in JMB: http://dx.doi.org/10.1016/j.jmb.2010.01.074

All modelling performed in poing: https://sourceforge.net/projects/poing/

Macromolecular crowding has a profound effect upon biochemical processes in the cell. We have computationally studied the effect of crowding upon protein folding for 12 small domains in a simulated
cell, using a coarse-grained protein model based upon Langevin dynamics designed to unify the often disjoint goals of protein folding simulation and structure prediction. The model can make predictions of native conformation with an accuracy comparable to the best current template-free models. It is fast enough to enable a more extensive analysis of crowding than previously attempted, studing several proteins at many different crowding levels, and further random repetitions designed to more closely approximate the ensemble of conformations. We find that when crowding approaches 40% excluded volume, the maximum level found in the cell, proteins fold to fewer native-like states. Notably, when
crowding is increased beyond this level, there is a sudden failure of protein folding: proteins fix upon a structure more quickly, and become trapped in extended conformations. These results suggest that the ability of small protein domains to fold without the help of chaperones may be an important factor in limiting the degree of macromolecular crowding in the cell. We discuss the possible implications
regarding the relationship between protein expression level, protein size, chaperone activity and aggregation.

Category:

Science & Technology

Tags:

• protein folding
• macromolecular crowding
• simulation
• bioinformatics
• computational biochemistry
• molecular dynamics

[rnjn1234]

yes i read this paper.....i am gonna present this paper in journal club! :)..

[benlablondon]

@rnjn1234 That's great, I'm glad you found the paper interesting!

[Omatollis]

Fuck yeah!