Institute of Physical Chemistry, Karlsruhe Institute of Technology (KIT), 76131 Karlsruhe, Germany.
Phys Chem Chem Phys. 2018 Jun 13;20(23):16222-16230. doi: 10.1039/c8cp01325j.
The thiol-disulfide exchange reaction in model systems and small peptides was investigated by means of a combined QM/MM metadynamics scheme. The free energy landscapes of these systems were generated, providing the structures of reactants and products with atomic detail, as well as the heights of free energy barriers (or, activation energies) opposing the spontaneous exchange. A QM/MM scheme with purely classical water turned out to be an efficient and accurate compromise solution. The calculations yielded the expected symmetric trisulfide transition state at S-S distances of 2.7 Å, interestingly, with a slight deviation from linearity at an S-S-S angle of 165°. The structure of the transition state as well as the free energy barrier were very similar for the intramolecular thiol-disulfide reactions in model peptides. While CXC disulfide bonds were found sterically unfavorable, CXXC were favored over longer-range disulfide bonds along the peptide backbone, in line with the high abundance of CXXC motifs in redox proteins.
通过 QM/MM 组合的 Metadynamics 方案研究了模型系统和小肽中的巯基-二硫键交换反应。生成了这些系统的自由能景观，提供了反应物和产物的原子细节结构，以及反对自发交换的自由能势垒（或活化能）的高度。事实证明，具有纯经典水的 QM/MM 方案是一种高效且准确的折衷解决方案。计算得出了预期的对称三硫化物过渡态，其 S-S 距离为 2.7 Å，有趣的是，S-S-S 角略有偏离线性，为 165°。对于模型肽中的分子内巯基-二硫键反应，过渡态的结构和自由能势垒非常相似。虽然 CXC 二硫键被认为是空间不利的，但 CXXC 比沿肽主链的长程二硫键更有利，这与氧化还原蛋白中 CXXC 基序的高丰度一致。
