Yun R H, Hermans J
Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina, Chapel Hill 27599-7260.
Protein Eng. 1991 Oct;4(7):761-6. doi: 10.1093/protein/4.7.761.
The conformational probability distribution of a valine residue in the valine dipeptide and of the valine side chain in an alpha-helix, as well as the change in helix stability for replacing alanine with valine, has been calculated by molecular dynamics simulations of explicitly hydrated systems: dipeptide, tetrapeptide and 10-, 14- and 18-residue oligoalanine helices. All computed free-energy differences are means from at least eight separate slow-growth simulations, four in each direction and are reported with their root-mean-square deviations. Different values for the change in free energy of folding (delta delta G degrees) have been calculated with the use of forcefields having an all-atom and a central-atom representation of methyl groups, etc. The value obtained with the all-atom forcefield agrees well with new experimental values (3 kJ/mol = 0.7 kcal/mol). Furthermore, the most stable valine side-chain rotamer in the helix is different for these two representations. The most stable rotamer for the all atom conformation is the same one that predominates for valines in alpha-helices in proteins of known conformation. The lower conformational freedom of the valine side chain in the helix contributes 1 kJ/mol to the difference in stability computed with the all-atom potential; unfavorable interactions of the side chain with helix, even in the most stable conformation, further increase delta delta G degrees.
通过对明确水合系统（二肽、四肽以及10、14和18个残基的寡聚丙氨酸螺旋）进行分子动力学模拟，计算了缬氨酸二肽中缬氨酸残基以及α-螺旋中缬氨酸侧链的构象概率分布，以及用缬氨酸取代丙氨酸时螺旋稳定性的变化。所有计算得到的自由能差均为至少八次独立的缓慢增长模拟的平均值，每个方向各四次，并报告其均方根偏差。使用具有甲基等全原子和中心原子表示的力场计算了折叠自由能变化（ΔΔG°）的不同值。用全原子力场得到的值与新的实验值（3 kJ/mol = 0.7 kcal/mol）吻合良好。此外，对于这两种表示，螺旋中最稳定的缬氨酸侧链旋转异构体是不同的。全原子构象中最稳定的旋转异构体与已知构象蛋白质中α-螺旋缬氨酸中占主导的旋转异构体相同。螺旋中缬氨酸侧链较低的构象自由度对用全原子势计算的稳定性差异贡献了1 kJ/mol；即使在最稳定的构象中，侧链与螺旋的不利相互作用也进一步增加了ΔΔG°。
