Belohorcová K, Davis J H, Woolf T B, Roux B
Department of Physics, University of Guelph, Ontario, Canada.
Biophys J. 1997 Dec;73(6):3039-55. doi: 10.1016/S0006-3495(97)78332-2.
A molecular dynamics simulation of a simple model membrane system composed of a single amphiphilic helical peptide (ace-K2GL16K2A-amide) in a fully hydrated 1,2-dimyristoyl-sn-glycero-3-phosphocholine bilayer was performed for a total of 1060 ps. The secondary structure of the peptide and its stability were described in terms of average dihedral angles, phi and psi, and the C alpha torsion angles formed by backbone atoms; by the average translation per residue along the helix axis; and by the intramolecular peptide hydrogen bonds. The results indicated that residues 6 through 15 remain in a stable right-handed alpha-helical conformation, whereas both termini exhibit substantial fluctuations. A change in the backbone dihedral angles for residues 16 and 17 is accompanied by the loss of two intramolecular hydrogen bonds, leading to a local but long-lived disruption of the helix. The dynamics of the peptide was characterized in terms of local and global helix motions. The local motions of the N-H bond angles were described in terms of the autocorrelation functions of P2[cos thetaNH(t, t + tau)] and reflected the different degrees of local peptide order as well as a variation in time scale for local motions. The chi1 and chi2 dihedral angles of the leucine side chains underwent frequent transitions between potential minima. No connection between the side-chain positions and their mobility was observed, however. In contrast, the lysine side chains displayed little mobility during the simulation. The global peptide motions were characterized by the tilting and bending motions of the helix. Although the peptide was initially aligned parallel to the bilayer normal, during the simulation it was observed to tilt away from the normal, reaching an angle of approximately 25 degrees by the end of the simulation. In addition, a slight bend of the helix was detected. Finally, the solvation of the peptide backbone and side-chain atoms was also investigated.
对一个简单的模型膜系统进行了分子动力学模拟，该系统由单个两亲性螺旋肽（ace-K2GL16K2A-酰胺）在完全水合的1,2-二肉豆蔻酰-sn-甘油-3-磷酸胆碱双层膜中组成，总共进行了1060皮秒。肽的二级结构及其稳定性通过平均二面角（φ和ψ）以及主链原子形成的Cα扭转角来描述；通过每个残基沿螺旋轴的平均平移来描述；并通过分子内肽氢键来描述。结果表明，6至15位残基保持稳定的右手α-螺旋构象，而两个末端表现出明显的波动。16和17位残基的主链二面角变化伴随着两个分子内氢键的丧失，导致螺旋局部但长期的破坏。肽的动力学通过局部和全局螺旋运动来表征。N-H键角的局部运动通过P2[cosθNH(t, t + τ)]的自相关函数来描述，反映了局部肽有序度的不同程度以及局部运动时间尺度的变化。亮氨酸侧链的χ1和χ2二面角在势能极小值之间频繁转换。然而，未观察到侧链位置与其流动性之间的联系。相比之下，赖氨酸侧链在模拟过程中显示出很少的流动性。全局肽运动通过螺旋的倾斜和弯曲运动来表征。尽管肽最初与双层法线平行排列，但在模拟过程中观察到它从法线倾斜，到模拟结束时达到约25度的角度。此外，检测到螺旋有轻微弯曲。最后，还研究了肽主链和侧链原子的溶剂化情况。
