Pasquier Coralie, Vazdar Mario, Forsman Jan, Jungwirth Pavel, Lund Mikael
Division of Theoretical Chemistry, Lund University , POB 124, SE-22100 Lund, Sweden.
Division of Organic Chemistry and Biochemistry, Rudjer Bošković Institute , POB 180, HR-10002 Zagreb, Croatia.
J Phys Chem B. 2017 Apr 13;121(14):3000-3006. doi: 10.1021/acs.jpcb.7b01051. Epub 2017 Mar 31.
The stability of aqueous protein solutions is strongly affected by multivalent ions, which induce ion-ion correlations beyond the scope of classical mean-field theory. Using all-atom molecular dynamics (MD) and coarse grained Monte Carlo (MC) simulations, we investigate the interaction between a pair of protein molecules in 3:1 electrolyte solution. In agreement with available experimental findings of "reentrant protein condensation", we observe an anomalous trend in the protein-protein potential of mean force with increasing electrolyte concentration in the order: (i) double-layer repulsion, (ii) ion-ion correlation attraction, (iii) overcharge repulsion, and in excess of 1:1 salt, (iv) non Coulombic attraction. To efficiently sample configurational space we explore hybrid continuum solvent models, applicable to many-protein systems, where weakly coupled ions are treated implicitly, while strongly coupled ones are treated explicitly. Good agreement is found with the primitive model of electrolytes, as well as with atomic models of protein and solvent.
蛋白质水溶液的稳定性受到多价离子的强烈影响，多价离子会引发超出经典平均场理论范围的离子-离子相关性。我们使用全原子分子动力学（MD）和粗粒化蒙特卡罗（MC）模拟，研究了3:1电解质溶液中一对蛋白质分子之间的相互作用。与“折返式蛋白质凝聚”的现有实验结果一致，我们观察到平均力的蛋白质-蛋白质势随电解质浓度增加呈现出异常趋势：（i）双层排斥，（ii）离子-离子相关性吸引，（iii）过电荷排斥，以及在超过1:1盐的情况下，（iv）非库仑吸引。为了有效地采样构型空间，我们探索了适用于多蛋白质系统的混合连续溶剂模型，其中弱耦合离子被隐式处理，而强耦合离子被显式处理。结果发现，该模型与电解质的原始模型以及蛋白质和溶剂的原子模型都有很好的一致性。
