Bille Anna, Linse Björn, Mohanty Sandipan, Irbäck Anders
Computational Biology and Biological Physics, Department of Astronomy and Theoretical Physics, Lund University, Sölvegatan 14A, SE-223 62 Lund, Sweden.
Institute for Advanced Simulation, Jülich Supercomputing Centre, Forschungszentrum Jülich, D-52425 Jülich, Germany.
J Chem Phys. 2015 Nov 7;143(17):175102. doi: 10.1063/1.4934997.
While steric crowders tend to stabilize globular proteins, it has been found that protein crowders can have an either stabilizing or destabilizing effect, where a destabilization may arise from nonspecific attractive interactions between the test protein and the crowders. Here, we use Monte Carlo replica-exchange methods to explore the equilibrium behavior of the miniprotein trp-cage in the presence of protein crowders. Our results suggest that the surrounding crowders prevent trp-cage from adopting its global native fold, while giving rise to a stabilization of its main secondary-structure element, an α-helix. With the crowding agent used (bovine pancreatic trypsin inhibitor), the trp-cage-crowder interactions are found to be specific, involving a few key residues, most of which are prolines. The effects of these crowders are contrasted with those of hard-sphere crowders.
虽然空间拥挤剂往往会使球状蛋白质稳定，但人们发现蛋白质拥挤剂可能具有稳定或不稳定的作用，其中不稳定可能源于测试蛋白质与拥挤剂之间的非特异性吸引相互作用。在这里，我们使用蒙特卡罗复制交换方法来探索在存在蛋白质拥挤剂的情况下小蛋白色氨酸笼的平衡行为。我们的结果表明，周围的拥挤剂阻止色氨酸笼形成其全局天然折叠，同时使其主要二级结构元件α螺旋稳定。使用的拥挤剂（牛胰蛋白酶抑制剂）时，发现色氨酸笼与拥挤剂的相互作用是特异性的，涉及几个关键残基，其中大多数是脯氨酸。将这些拥挤剂的作用与硬球拥挤剂的作用进行了对比。
