Polymer models of protein stability, folding, and interactions.
The unfolded state and flexible linkers in the folded structure play essential roles in protein stability and folding and protein-protein interactions. Intrinsic to these roles is the fact that unfolded proteins and flexible linkers sample many different conformations. Polymer models may capture this and complement experiments in elucidating the contributions of the unfolded state and flexible linkers. Here I review what can be predicted from these models and how well these predictions match experiments. For example, Gaussian chain models give quantitatively reasonable predictions of the effects of residual charge-charge interactions in the unfolded state and qualitatively reasonable results for the effects of spatial confinement and macromolecular crowding on protein stability. A wormlike chain model has met with success in quantifying the effects of flexible linkers in binding affinity enhancement and in regulatory switches. In future developments, more realistic models may emerge from molecular dynamics simulations, and these models will guide experiments to advance our understanding of the unfolded state and flexible linkers.
Department of Physics and Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida 32306, USA. zhou@sb.fsu.edu
Huan-Xiang
HX
Zhou
D000818:Animals; D003198:Computer Simulation; D006801:Humans; D008956:Models, Chemical; D008958:Models, Molecular; D011108:Polymers / Q000737:chemistry*; D017510:Protein Folding; D025941:Protein Interaction Mapping / Q000379:methods*; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
D011108:Polymers; D011506:Proteins