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 (ΔAi) and structures are analyzed as a function of the reduced second virial coefficient b2∗. ΔAi values and the average structures of clusters up to pentamers have distinct differences due to the anisotropic nature of the dipolar interactions. However, ΔAi values can be mapped semiquantitatively between the two cases if compared at common values of b2∗. 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.
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机译:弱关联的蛋白质寡聚物或簇的可逆形成是诸如蛋白质聚集和胶体相分离等过程中的关键早期步骤。先前开发的基于细胞的晶格流体准化学模型[T. M. Young和C. J. Roberts,J。Chem。物理127,165101(2007)]扩展到此处以处理连续空间系统。它通过在等电点使用两种简化的球形蛋白质极限情况进行了说明:具有各向同性短程吸引的球形方阱(SW)粒子和具有SW吸引和方肩排斥力的筛选偶极粒子。根据减少的第二维里系数b2 *分析簇自由能(ΔAi)和结构。由于偶极相互作用的各向异性,ΔAi值和高达五聚体的簇的平均结构具有明显的差异。但是,如果与b2 *的公共值进行比较,则可以在两种情况之间半定量地映射ΔAi值。构造了低聚的自由能景观,说明了偶极流体与西南流体的小簇在景观坚固性方面的显着差异,并为蛋白质成核依赖性聚集的经验模型提出了可能的分子解释。
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