Competition between folding and aggregation in a model for protein solutions
Theoretical Sciences Unit, JNCASR, 560065, Bangalore, India
2 Raman Research Institute, C.V. Raman Avenue, 560080, Bangalore, India
3 National Centre for Biological Sciences (TIFR), Bellary Road, 560065, Bangalore, India
Accepted: 18 May 2010
Published online: 22 June 2010
We study the thermodynamic and kinetic consequences of the competition between single-protein folding and protein-protein aggregation using a phenomenological model, in which the proteins can be in the unfolded (U), misfolded (M) or folded (F) states. The phase diagram shows the coexistence between a phase with aggregates of misfolded proteins and a phase of isolated proteins (U or F) in solution. The spinodal at low protein concentrations shows non-monotonic behavior with temperature, with implications for the stability of solutions of folded proteins at low temperatures. We follow the dynamics upon “quenching” from the U-phase (cooling) or the F-phase (heating) to the metastable or unstable part of the phase diagram that results in aggregation. We describe how interesting consequences to the distribution of aggregate size, and growth kinetics arise from the competition between folding and aggregation.
© EDP Sciences, SIF, Springer-Verlag Berlin Heidelberg, 2010