Molecular dynamics simulations of three protegrin-type antimicrobial peptides:: interplay between charges at the termini, β-sheet structure and amphiphilic interactions
Molecular dynamics simulations of three protegrin-type antimicrobial peptides:: interplay between charges at the termini, β-sheet structure and amphiphilic interactions
复制标题
DOI：
10.1080/08927020701393481
复制
发表时间：
2007-01-01
影响因子：
2.1
通讯作者：
Kaznessis, Y. N.
中科院分区：
文献类型：
--
作者：
Bolintineanu, D. S.;Langham, A. A.;Kaznessis, Y. N.
我们已经进行了分子动力学模拟的天然存在的保护蛋白PG-1肽和它的两个突变体，PC-9和PC-13在十二烷基磷酸胆碱（DPC）胶束的存在下。分析了在PC-9的情况下破坏β-折叠结构和在PC-13的情况下减少C-末端电荷的突变的影响。结果发现，这两个突变的肽的表面结合的构象受到严重影响。PG- 1的C-末端和β-发夹弯与胶束脂质头基强烈相互作用，而其N-末端链弯曲远离胶束并驻留在水相区域; PC-13的N-末端和β-发夹弯区域与胶束强烈相互作用，同时保持比PG- 1紧密得多的构象;相对于同源PG- 1结构，PC-9实现了高度扭曲的构象，这允许其末端和β-发夹区域与胶束相互作用。这些显着的差异，观察到的结果，看似微小的突变的序列的三个肽的残基电荷，结构刚性和两亲性相互作用之间的相互作用的解释。保守的推断，桥接这些生物物理相互作用和药理学的肽。
We have carried out molecular dynamics simulations of the naturally occurring protegrin PG-1 peptide and two of its mutants, PC-9 and PC-13 in the presence of a dodecyl-phosphocholine ( DPC) micelle. The effects of mutations that disrupt the beta-sheet structure in the case of PC-9 and reduce the charge at the C-terminus in the case of PC-13 are analyzed. It is found that the surface-bound conformations of the peptides are severely affected by both mutations. PG- 1 exhibits a conformation in which the C-terminus and the beta- hairpin turn interact strongly with the micelle lipid head groups, while its N- terminal strand bends away from the micelle and resides in the aqueous region; PC-13 exhibits strong interactions with the micelle at its N- terminus as well as the beta- hairpin turn region, while retaining a much more compact conformation than PG- 1; PC-9 achieves a highly distorted conformation relative to the homologous PG- 1 structure, which allows both its termini and the beta- hairpin region to interact with the micelle. These significant differences observed as a result of seemingly minor mutations to the sequences of the three peptides are explained in terms of the interplay between residue charges, structural rigidity and amphiphilic interactions. Conservative inferences are made bridging these biophysical interactions and the pharmacological profiles of the peptides.