Lomize A L, Mosberg H I
College of Pharmacy, University of Michigan, Ann Arbor 48109, USA.
Biopolymers. 1997 Aug;42(2):239-69. doi: 10.1002/(SICI)1097-0282(199708)42:2<239::AID-BIP12>3.0.CO;2-G.
A thermodynamic model describing formation of alpha-helices by peptides and proteins in the absence of specific tertiary interactions has been developed. The model combines free energy terms defining alpha-helix stability in aqueous solution and terms describing immersion of every helix or fragment of coil into a micelle or a nonpolar droplet created by the rest of protein to calculate averaged or lowest energy partitioning of the peptide chain into helical and coil fragments. The alpha-helix energy in water was calculated with parameters derived from peptide substitution and protein engineering data and using estimates of nonpolar contact areas between side chains. The energy of nonspecific hydrophobic interactions was estimated considering each alpha-helix or fragment of coil as freely floating in the spherical micelle or droplet, and using water/cyclohexane (for micelles) or adjustable (for proteins) side-chain transfer energies. The model was verified for 96 and 36 peptides studied by 1H-nmr spectroscopy in aqueous solution and in the presence of micelles, respectively ([set 1] and [set 2]) and for 30 mostly alpha-helical globular proteins ([set 3]). For peptides, the experimental helix locations were identified from the published medium-range nuclear Overhauser effects detected by 1H-nmr spectroscopy. For sets 1, 2, and 3, respectively, 93, 100, and 97% of helices were identified with average errors in calculation of helix boundaries of 1.3, 2.0, and 4.1 residues per helix and an average percentage of correctly calculated helix-coil states of 93, 89, and 81%, respectively. Analysis of adjustable parameters of the model (the entropy and enthalpy of the helix-coil transition, the transfer energy of the helix backbone, and parameters of the bound coil), determined by minimization of the average helix boundary deviation for each set of peptides or proteins, demonstrates that, unlike micelles, the interior of the effective protein droplet has solubility characteristics different from that for cyclohexane, does not bind fragments of coil, and lacks interfacial area.
已开发出一种热力学模型，用于描述在不存在特定三级相互作用的情况下，肽和蛋白质形成α-螺旋的过程。该模型结合了定义α-螺旋在水溶液中稳定性的自由能项，以及描述每个螺旋或卷曲片段浸入由蛋白质其余部分形成的胶束或非极性液滴中的项，以计算肽链在螺旋和卷曲片段中的平均或最低能量分配。水中α-螺旋的能量是通过从肽取代和蛋白质工程数据中得出的参数，并利用侧链之间非极性接触面积的估计值来计算的。非特异性疏水相互作用的能量是通过将每个α-螺旋或卷曲片段视为自由漂浮在球形胶束或液滴中，并利用水/环己烷（用于胶束）或可调的（用于蛋白质）侧链转移能量来估计的。该模型分别针对在水溶液中和存在胶束的情况下通过1H-核磁共振光谱研究的96个和36个肽（[组1]和[组2]）以及针对30个主要为α-螺旋的球状蛋白质（[组3]）进行了验证。对于肽，通过1H-核磁共振光谱检测到的已发表的中程核Overhauser效应来确定实验性螺旋位置。对于组1、组2和组3，分别有93%、100%和97%的螺旋被识别出来，每个螺旋的螺旋边界计算平均误差分别为每螺旋1.3、2.0和4.1个残基，正确计算的螺旋-卷曲状态的平均百分比分别为93%、89%和81%。通过最小化每组肽或蛋白质的平均螺旋边界偏差来确定模型的可调参数（螺旋-卷曲转变的熵和焓、螺旋主链的转移能量以及结合卷曲的参数），结果表明，与胶束不同，有效蛋白质液滴的内部具有与环己烷不同的溶解性特征，不结合卷曲片段，并且缺乏界面面积。
