Wang C Y, Yang C F, Lai M C, Lee Y H, Lee T L, Lin T H
Institute of Biomedical Science, National Tsing Hua University, Taiwan, Republic of China.
Biopolymers. 1994 Aug;34(8):1027-36. doi: 10.1002/bip.360340806.
We have used the molecular dynamics (MD) simulation package AMBER4 to search the conformation of a peptide predicted as a leucine zipper motif for the human immunodeficiency virus type 1 integrase protein (HIV IN-LZM). The peptide is composed of 22 amino acid residues and its location is from Val 151 to Leu 172. The searching procedure also includes two known alpha-helices that served as positive controls--namely, a 22-residue GCN4-p1 (LZM) and a 20-residue poly (L-alanine) (PLA). A 21-residue peptide extracted from a cytochrome C crystal (CCC-t) with determined conformation as a beta-turn is also included as a negative control. At the beginning of the search, two starting conformations--namely, the standard right-handed alpha-helix and the fully stretched conformations--are generated for each peptide. Structures generated as standard alpha-helix are equilibrated at room temperature for 90 ps while structures generated as a fully stretched one are equilibrated at 600 K for 120 ps. The CCC-t and PLA helices are nearly destroyed from the beginning of equilibration. However, for both the HIV IN-LZM and the GCN4-p1 LZM structures, there is substantial helicity being retained throughout the entire course of equilibration. Although helix propagation profiles calculated indicate that both peptides possess about the same propensity to form an alpha-helix, the HIV IN-LZM helix appears to be more stable than the GCN4-p1 one as judged by a variety of analyses on both structures generated during the equilibration course. The fact that predicted HIV IN-LZM can exist as an alpha-helix is also supported by the results of high temperature equilibration run on the fully stretched structures generated. In this run, the RMS deviations between the backbone atoms of the structures with the lowest potential energy (PE) identified within every 2 ps and the structure with the lowest PE searched in the same course of simulation are calculated. For both the HIV IN-LZM and the GCN4-p1 LZM, these rms values decrease with the decrease of PE, which indicates that both structures are closer in conformations as their PEs are moved deeper into the PE well.
我们使用分子动力学（MD）模拟软件包AMBER4来搜索一种被预测为人类免疫缺陷病毒1型整合酶蛋白（HIV IN-LZM）亮氨酸拉链基序的肽段的构象。该肽段由22个氨基酸残基组成，其位置从Val 151到Leu 172。搜索过程还包括两个已知的α-螺旋作为阳性对照——即一个22个残基的GCN4-p1（LZM）和一个20个残基的聚（L-丙氨酸）（PLA）。从细胞色素C晶体中提取的一个21个残基的肽段（CCC-t），其构象已确定为β-转角，也被用作阴性对照。在搜索开始时，为每个肽段生成两种起始构象——即标准的右手α-螺旋构象和完全伸展的构象。生成的标准α-螺旋结构在室温下平衡90皮秒，而生成的完全伸展结构在600 K下平衡120皮秒。CCC-t和PLA螺旋从平衡开始就几乎被破坏。然而，对于HIV IN-LZM和GCN4-p1 LZM结构，在整个平衡过程中都保留了相当程度的螺旋性。尽管计算得到的螺旋传播曲线表明这两种肽段形成α-螺旋的倾向大致相同，但通过对平衡过程中生成的两种结构进行的各种分析判断，HIV IN-LZM螺旋似乎比GCN4-p1螺旋更稳定。对生成的完全伸展结构进行高温平衡运行的结果也支持了预测的HIV IN-LZM可以以α-螺旋形式存在这一事实。在这次运行中，计算了每2皮秒内确定的具有最低势能（PE）的结构的主链原子与在同一模拟过程中搜索到的具有最低PE的结构之间的均方根偏差（RMS）。对于HIV IN-LZM和GCN4-p1 LZM，这些RMS值随着PE的降低而减小，这表明随着它们的PE向势能阱深处移动，两种结构的构象更接近。
