Institute of Advanced Energy, Kyoto University, Uji, Kyoto 611-0011, Japan.
J Chem Phys. 2010 Feb 14;132(6):065105. doi: 10.1063/1.3319509.
We have recently shown that protein folding is driven by the water-entropy gain. When the alpha-helix or beta-sheet is formed, the excluded volumes generated by the backbone and side chains overlap, leading to an increase in the total volume available to the translational displacement of water molecules. Primarily by this effect, the water entropy becomes higher. At the same time, the dehydration penalty (i.e., the break of hydrogen bonds with water molecules) is compensated by the formation of intramolecular hydrogen bonds. Hence, these secondary structures are very advantageous units, which are to be formed as much as possible in protein folding. The packing of side chains, which leads to a large increase in the water entropy, is also crucially important. Here we investigate the roles of the side-chain packing in the second structural preference in protein folding. For some proteins we calculate the hydration entropies of a number of structures including the native structure with or without side chains. A hybrid of the angle-dependent integral equation theory combined with the multipolar water model and the morphometric approach is employed in the calculation. Our major findings are as follows. For the structures without side chains, there is an apparent tendency that the water entropy becomes higher as the alpha-helix or beta-sheet content increases. For the structures with side chains, however, a higher content of alpha-helices or beta-sheets does not necessarily lead to larger entropy of water due to the effect of the side-chain packing. The thorough, overall packing of side chains, which gives little space in the interior, is unique to the native structure. To accomplish such specific packing, the alpha-helix and beta-sheet contents are prudently adjusted in protein folding.
我们最近表明，蛋白质折叠是由水熵增益驱动的。当α-螺旋或β-折叠形成时，由骨架和侧链产生的排除体积重叠，导致水分子平移位移的可用总容积增加。主要通过这种效应，水熵变得更高。同时，通过形成分子内氢键来补偿脱水罚分（即与水分子的氢键断裂）。因此，这些二级结构是非常有利的单元，在蛋白质折叠中尽可能多地形成。导致水熵大幅增加的侧链堆积也至关重要。在这里，我们研究了侧链堆积在蛋白质折叠中二结构偏好中的作用。对于一些蛋白质，我们计算了包括带有或不带侧链的天然结构在内的多种结构的水合熵。在计算中采用了角度相关积分方程理论与多极水分子模型和形态计量方法的混合。我们的主要发现如下。对于没有侧链的结构，随着α-螺旋或β-折叠含量的增加，水熵明显升高。然而，对于带有侧链的结构，由于侧链堆积的影响，较高的α-螺旋或β-折叠含量不一定导致更大的水熵。彻底的、全面的侧链堆积，内部几乎没有空间，这是天然结构所特有的。为了完成这种特定的堆积，在蛋白质折叠中谨慎地调整α-螺旋和β-折叠的含量。
