Spontaneous membrane-translocating peptide adsorption at silica surfaces: a molecular dynamics study.
Spontaneous membrane-translocating peptide adsorption at silica surfaces: a molecular dynamics study.
复制标题
DOI：
10.1021/jp409130s
复制
发表时间：
2013-11-27
期刊：
影响因子：
--
通讯作者：
Mulheran PA
中科院分区：
文献类型：
--
作者：
Kubiak-Ossowska K;Burley G;Patwardhan SV;Mulheran PA
自发膜转运肽（SMTPs）最近被证明可以直接穿透细胞膜。本文利用完全原子分子动力学模拟研究了SMTP和一些工程扩展在模型二氧化硅表面的吸附，以评估它们构建新型药物传递系统的潜力。模拟重现了单一富硅氧体带电表面上的电场，轨迹表明吸附的主要驱动力是静电。盐浓度的增加减慢但不阻止SMTP在表面的吸附；它也不会导致肽的解吸，表明通过疏水力进行额外的结合。结果用于设计肽序列的扩展，我们发现这些扩展增强了吸附，但不影响吸附的构象。我们还研究了表面羟基化对肽吸附的影响。在所有情况下，最终吸附的构象都是肽与精氨酸残基平展到表面的构象，精氨酸残基是肽功能的关键，将肽固定在表面，使其不暴露于溶液中。这种构象可能影响它们在膜易位中的作用，因此对未来药物传递载体的设计具有重要意义。
Spontaneous membrane-translocating peptides (SMTPs) have recently been shown to directly penetrate cell membranes. Adsorption of a SMTP, and some engineered extensions, at model silica surfaces is studied herein using fully atomistic molecular dynamics simulations in order to assess their potential to construct novel drug delivery systems. The simulations are designed to reproduce the electric fields above single, siloxide-rich charged surfaces, and the trajectories indicate that the main driving force for adsorption is electrostatic. An increase in the salt concentration slows down but does not prevent adsorption of the SMTP to the surface; it also does not result in peptide desorption, suggesting additional binding via hydrophobic forces. The results are used to design extensions to the peptide sequence which we find enhance adsorption but do not affect the adsorbed conformation. We also investigate the effect of surface hydroxylation on the peptide adsorption. In all cases, the final adsorbed conformations are with the peptide flattened to the surface with arginine residues, which are key to the peptide’s function, anchoring it to the surface so that they are not exposed to solution. This conformation could impact their role in membrane translocation and thus has important implications for the design of future drug delivery vehicles.
登录
查看更多内容
什么控制蛋白质在带电固体表面的吸附和固定？
DOI：
10.1021/la101276v
发表时间：
2010-06-01
期刊：
Langmuir : the ACS journal of surfaces and colloids
影响因子：
--
作者：
Kubiak-Ossowska K;Mulheran PA
通讯作者：
Mulheran PA
影响因子：
7.3
作者：
Heitz F;Morris MC;Divita G
通讯作者：
Divita G
影响因子：
3.3
作者：
Kubiak-Ossowska, Karina;Mulheran, Paul A.
通讯作者：
Mulheran, Paul A.
影响因子：
3.9
作者：
Kubiak-Ossowska, Karina;Mulheran, Paul A.
通讯作者：
Mulheran, Paul A.
DOI：
10.1016/j.bbrc.2012.01.041
发表时间：
2012-02-17
影响因子：
3.1
作者：
Amand, Helene L.;Norden, Bengt;Fant, Kristina
通讯作者：
Fant, Kristina