Department of Chemical Engineering, Lehigh University, Bethlehem, Pennsylvania, USA.
Biophys J. 2010 Jan 20;98(2):315-20. doi: 10.1016/j.bpj.2009.10.009.
We investigate the effect of macromolecular crowding on protein folding, using purely repulsive crowding particles and a self-organizing polymer model of protein folding. We find that the variation in folding stability with crowder size for typical alpha-, beta-, and alpha/beta-proteins is well described by an adaptation of the scaled particle theory. The native state, the transition state, and the unfolded protein are treated as effective hard spheres, with the folded and transition state radii independent of the size and concentration of the crowders. Remarkably, we find that, as the effective unfolded state radius is very weakly dependent on the crowder concentration, it can also be approximated by a single size. The same model predicts the effect of crowding on the folding barrier and therefore refolding rates with no adjustable parameters. A simple extension of the scaled-particle theory model, assuming additivity, can also describe the behavior of mixtures of crowding particles.
我们使用纯粹的排斥性拥挤粒子和蛋白质折叠的自组织聚合物模型来研究大分子拥挤对蛋白质折叠的影响。我们发现，典型的α-、β-和α/β-蛋白质的折叠稳定性随拥挤剂大小的变化可以很好地用扩展的标度粒子理论来描述。天然状态、过渡状态和未折叠的蛋白质被视为有效的硬球，折叠状态和过渡状态的半径与拥挤剂的大小和浓度无关。值得注意的是，我们发现，由于有效未折叠状态半径对拥挤剂浓度的依赖性非常弱，因此也可以用单一尺寸来近似。同样的模型预测了拥挤对折叠势垒的影响，因此也预测了再折叠速率，无需可调参数。扩展的标度粒子理论模型的一个简单扩展，假设加和性，也可以描述拥挤粒子混合物的行为。
