Structure and thermodynamics of colloidal protein cluster formation: comparison of square-well and simple dipolar models.
Reversible formation of weakly associated protein oligomers or clusters is a key early step in processes such as protein aggregation and colloidal phase separation. A previously developed cell-based, quasichemical model for lattice fluids [T. M. Young and C. J. Roberts, J. Chem. Phys. 127, 165101 (2007)] is extended here to treat continuous-space systems. It is illustrated using two simplified limiting cases for globular proteins at the isoelectric point: spherical square-well (SW) particles with an isotropic short-ranged attraction and screened dipolar particles with SW attractions and square-shoulder repulsions. Cluster free energies (DeltaA(i)) and structures are analyzed as a function of the reduced second virial coefficient b(2)(*). DeltaA(i) values and the average structures of clusters up to pentamers have distinct differences due to the anisotropic nature of the dipolar interactions. However, DeltaA(i) values can be mapped semiquantitatively between the two cases if compared at common values of b(2)(*). Free energy landscapes of oligomerization are constructed, illustrating significant differences in landscape ruggedness for small clusters of dipolar versus SW fluids, and suggesting a possible molecular interpretation for empirical models of nucleation-dependent aggregation of proteins.
Department of Chemical Engineering, University of Delaware, 150 Academy St., Newark, Delaware 19716, USA.
Teresa M
TM
Young
Christopher J
CJ
Roberts
D003102:Colloids / Q000737:chemistry*; D003198:Computer Simulation; D008956:Models, Chemical; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000648:ultrastructure*; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D013816:Thermodynamics
D003102:Colloids; D046912:Multiprotein Complexes; D011506:Proteins