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首页> 外文期刊>RSC Advances >Estimation of a stronger heparin binding locus in fibronectin domain III14 using thermodynamics and molecular dynamics
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Estimation of a stronger heparin binding locus in fibronectin domain III14 using thermodynamics and molecular dynamics

机译：使用热力学和分子动力学估计纤连蛋白域III14中较强的肝素结合轨迹

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The HEP II (Heparin-binding site II) region of fibronectin (FN) containing domain III ~(14) plays a crucial role in cell adhesion and migration through heparin-binding on the cell surface. There are two such fibronectin heparin interacting peptide (FHIP I and FHIP II) sequences present in HEP II. However, the molecular principles by which these sites orchestrate heparin-binding processes are poorly understood. Such knowledge would have great implications in the therapeutic targeting of FN. With this aim, we have explored the binding studies of FHIP I and FHIP II with heparin using various biophysical methods. A fluorescence melting study specifically revealed the preference of heparin for domain III in FN, indicating the key contribution of FHIP I and FHIP II in heparin binding. In isothermal titration calorimetry (ITC), the higher binding affinity observed for FHIP II (～10 ~(7) mol ~(?1) ) compared to FHIP I (～10 ~(6) mol ~(?1) ) is expected due to the presence of a superior cluster of Arg and Lys residues in FHIP II, which can facilitate specific H-bonding interactions with heparin. Based on heat capacity changes, the key role of H-bonding, electrostatic and hydrophobic interactions was demonstrated in binding. Finally, the molecular docking and MD simulation results reinforced that the interaction of heparin (dodecasaccharide) is stronger and stable with the FHIP II peptide. The results described here suggest that these peptides provide all the structural and thermodynamic elements necessary for heparin-binding of HEP II of FN. Subsequently, it can be concluded that FHIP II could be a better location for therapeutic intervention in cell adhesion activity by FN.
机译：含有结构域III〜（14）的纤连蛋白（Fn）的HEPI（肝素结合位点II）区域在细胞粘附和迁移通过细胞表面上的肝素结合起到至关重要的作用。存在两种这样的纤连蛋白肝素相互作用肽（PEP I和PHEP II）序列存在于HEP II中。然而，这些位点协调肝素结合过程的分子原理是较差的。这些知识将对FN的治疗靶向具有很大的影响。通过此目的，我们探讨了使用各种生物物理方法的肝素与肝素的FHIP I和PHIP的结合研究。荧光熔化研究特别揭示了肝素在FN中的肝素III的偏好，表明肝素结合中的PHIP I和PHIP II的关键贡献。在等温滴定热量（ITC）中，与PHIP I相比，针对FHIP II的较高的结合亲和力（〜10〜（7）mol〜（？1））预计预期（〜10〜（6）mol〜（？1））由于施法II的优异的Arg和Lys残基存在，这可以促进与肝素的特异性H键合相互作用。基于热容量的变化，在结合中证明了H键合，静电和疏水相互作用的关键作用。最后，分子对接和MD仿真结果增强了肝素（十二烷糖）的相互作用与FHIP II肽具有较强且稳定的。这里描述的结果表明，这些肽提供了肝素结合Fn的肝素结合所必需的所有结构和热力学元素。随后，可以得出结论，施法II可以是通过FN的细胞粘附活性治疗干预的更好位置。

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