Shao Qiang
Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road, Shanghai 201203, China.
J Phys Chem B. 2014 Jun 12;118(23):6175-85. doi: 10.1021/jp500280v. Epub 2014 May 30.
Mixtures of osmolytes are present in the cell. Therefore, the understanding of the interplay of mixed osmolyte molecules and their combined effects on protein structure is of fundamental importance. In this article, the structure stability of a model protein (BdpA) in the mixture of guanidinium thiocyanate (GdmSCN) and methanol (MeOH) was investigated by molecular dynamics simulation. It was observed that guanidinium (Gdm(+)) is driven to protein surface by favorable electrostatic interactions and MeOH is driven by both favorable electrostatic and VDW interactions, respectively. The mixture of Gdm(+) and MeOH doesnot affect the electrostatic energy distribution of Gdm(+) but does reduce the difference in VDW energy of MeOH between the regions of protein surface and bulk solution. As a result, the accumulation level of Gdm(+) is not influenced, but the accumulation level of MeOH is lowered in mixed solution. The tertiary structure stability of protein is determined by the accumulated strength of VDW interactions from MeOH to protein side chain, and the secondary structure stability is correlated to the strength of combined electrostatic energies from solvent (water) and cosolvent (Gdm(+) and MeOH) to protein backbone, particularly in hydrogen bonding part. The mixture of GdmSCN with low-concentrated MeOH stabilizes native structure of BdpA whereas the further increase of MeOH concentration denatures native structure of protein to expanded unfolded structure. The present study together with our previous study on the mixture of GdmSCN and 2,2,2-trifluoroethanol (TFE) provides novel insights into the effects of mixed osmolytes on protein structure.
细胞中存在渗透溶质混合物。因此，了解混合渗透溶质分子之间的相互作用及其对蛋白质结构的综合影响至关重要。在本文中，通过分子动力学模拟研究了模型蛋白（BdpA）在硫氰酸胍（GdmSCN）和甲醇（MeOH）混合物中的结构稳定性。观察到胍离子（Gdm(+)）通过有利的静电相互作用被驱动到蛋白质表面，而甲醇则分别通过有利的静电相互作用和范德华相互作用被驱动。Gdm(+)和MeOH的混合物不会影响Gdm(+)的静电能分布，但会减小蛋白质表面区域和本体溶液中甲醇的范德华能差异。结果，混合溶液中Gdm(+)的积累水平不受影响，但甲醇的积累水平降低。蛋白质的三级结构稳定性由甲醇与蛋白质侧链之间范德华相互作用的积累强度决定，二级结构稳定性与溶剂（水）和共溶剂（Gdm(+)和MeOH）与蛋白质主链的组合静电能强度相关，特别是在氢键部分。低浓度MeOH与GdmSCN的混合物可稳定BdpA的天然结构，而MeOH浓度的进一步增加会使蛋白质的天然结构变性为扩展的未折叠结构。本研究与我们之前关于GdmSCN和2,2,2-三氟乙醇（TFE）混合物的研究一起，为混合渗透溶质对蛋白质结构的影响提供了新的见解。
