Zangi Ronen
Department of Organic Chemistry I, University of the Basque Country UPV/EHU, Avenida de Tolosa 72, 20018, San Sebastian, Spain and IKERBASQUE, Basque Foundation for Science, 48011, Bilbao, Spain.
Phys Rev E Stat Nonlin Soft Matter Phys. 2014 Jan;89(1):012723. doi: 10.1103/PhysRevE.89.012723. Epub 2014 Jan 30.
Understanding the driving forces that lead to the stability of the secondary motifs found in proteins, namely α-helix and β-sheet, is a major goal in structural biology. The thermodynamic stability of these repetitive units is a result of a delicate balance between many factors, which in addition to the peptide chain involves also the solvent. Despite the fact that the backbones of all amino acids are the same (except of that of proline), there are large differences in the propensity of the different amino acids to promote the helical structure. In this paper, we investigate by explicit-solvent molecular dynamics simulations the role of the side chains (modeled as coarse-grained single sites) in stabilizing α helices in an aqueous solution. Our model systems include four (six-mer-nine-mer) peptide lengths in which the magnitude of the effective attraction between the side chains is systematically increased. We find that these interactions between the side chains can induce (for the nine-mer almost completely) a transition from a coil to a helical state. This transition is found to be characterized by three states in which the intermediate state is a partially folded α-helical conformation. In the absence of any interactions between the side chains the free energy change for helix formation has a small positive value indicating that favorable contributions from the side chains are necessary to stabilize the helical conformation. Thus, the helix-coil transition is controlled by the effective potentials between the side-chain residues and the magnitude of the required attraction per residue, which is on the order of the thermal energy, reduces with the length of the peptide. Surprisingly, the plots of the population of the helical state (or the change in the free energy for helix formation) as a function of the total effective interactions between the side chains in the helical state for all peptide lengths fall on the same curve.
理解导致蛋白质中二级基序（即α螺旋和β折叠）稳定性的驱动力是结构生物学的一个主要目标。这些重复单元的热力学稳定性是许多因素之间微妙平衡的结果，除了肽链外，还涉及溶剂。尽管所有氨基酸的主链都是相同的（除了脯氨酸），但不同氨基酸促进螺旋结构的倾向存在很大差异。在本文中，我们通过显式溶剂分子动力学模拟研究了侧链（建模为粗粒度单位点）在水溶液中稳定α螺旋的作用。我们的模型系统包括四种（六聚体 - 九聚体）肽长度，其中侧链之间有效吸引力的大小系统地增加。我们发现侧链之间的这些相互作用可以诱导（对于九聚体几乎完全）从卷曲态到螺旋态的转变。发现这种转变以三种状态为特征，其中中间状态是部分折叠的α螺旋构象。在侧链之间没有任何相互作用的情况下，螺旋形成的自由能变化具有小的正值，表明侧链的有利贡献对于稳定螺旋构象是必要的。因此，螺旋 - 卷曲转变由侧链残基之间的有效势控制，并且每个残基所需吸引力的大小（与热能相当）随着肽的长度而减小。令人惊讶的是，所有肽长度的螺旋态群体（或螺旋形成自由能的变化）作为螺旋态侧链之间总有效相互作用的函数的图落在同一条曲线上。
