Department of Chemical and Process Engineering, University of Strathclyde , James Weir Building, 75 Montrose Street, Glasgow G1 1XJ, United Kingdom.
J Phys Chem B. 2013 Nov 27;117(47):14666-75. doi: 10.1021/jp409130s. Epub 2013 Nov 15.
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.
最近已经证明，自发的膜穿透肽（SMTP）可以直接穿透细胞膜。本文使用全原子分子动力学模拟研究了在模型二氧化硅表面上的 SMTP 及其一些工程化延伸的吸附，以评估它们构建新型药物输送系统的潜力。这些模拟旨在复制单硅酸富电荷表面上方的电场，轨迹表明吸附的主要驱动力是静电。盐浓度的增加会减缓但不会阻止 SMTP 吸附到表面上；它也不会导致肽解吸，这表明通过疏水力还存在其他结合。这些结果被用于设计肽序列的延伸，我们发现这些延伸可以增强吸附，但不会影响吸附构象。我们还研究了表面羟基化对肽吸附的影响。在所有情况下，最终的吸附构象都是肽与表面平坦化，其中精氨酸残基是肽功能的关键，将其锚定在表面上，使其不暴露于溶液中。这种构象可能会影响它们在膜转位中的作用，因此对未来药物输送载体的设计具有重要意义。
