Investigating the Role of Phosphorylation in the Binding of Silaffin Peptide R5 to Silica with Molecular Dynamics Simulations
Investigating the Role of Phosphorylation in the Binding of Silaffin Peptide R5 to Silica with Molecular Dynamics Simulations
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DOI：
10.1021/acs.langmuir.7b02868
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发表时间：
2018-01-23
期刊：
影响因子：
3.9
通讯作者：
Pfaendtner, Jim
中科院分区：
文献类型：
--
作者：
Sprenger, K. G.;Prakash, Arushi;Pfaendtner, Jim
仿生二氧化硅的形成是一个主要由蛋白质驱动的过程，由于其在新生物技术发展中的作用，近年来引起了人们极大的兴趣。然而，许多仍然未知的分子尺度的机制，蛋白质结合到生物矿物表面，如二氧化硅，甚至关键的残留水平之间的相互作用，这样的蛋白质和表面。在这项研究中，我们采用分子动力学（MD）模拟研究的结合R5一个19个残基的天然silaffin肽段用于在体外二氧化硅形成的二氧化硅表面。采用后动力学增强取样方法，研究了中性（pH7.5）和酸性（pH5）条件下R5与SiO2的结合行为。结果显示了两种情况之间结合机制的根本差异，为R5和天然硅亲蛋白沉淀二氧化硅的pH依赖性能力提供了独特的见解。我们还研究了R5中丝氨酸残基的磷酸化对二氧化硅结合自由能和肽的界面构象的影响。结果表明，磷酸化通过引入电荷和空间位阻作用，显著降低了R5的结合自由能，改变了R5的结构。从这项工作中获得的新的机械见解可以为新生物材料和生物技术的合理设计提供信息。
Biomimetic silica forrnation, a process that is largely driven by proteins, has garnered considerable interest in recent years due to its role in the development Of new biotechnologies. However, much remains unknown of the molecular-scale mechanisms underlying the binding of proteins to biomineral surfaces such as silica, or even of the key residue-level interactions between,such proteins and surfaces. In this study, we employ molecular dynamics (MD) simulations to study the binding of R5 a 19-residue segment of a native silaffin peptide used for in vitro silica formation-to a silica surface. The metaclynamics enhanced Sampling methd is used to converge the binding behavior of R5 on silica at both neutral (pH 7.5) and acidic (pH 5) conditions. The results show fundamental differences in the mechanism of binding between the two cases, providing unique insight into the pH dependent ability of R5 and native silaffin to precipitate silica. We also study the effect of phosphorylation of serine residues in R5 on both the binding free energy to silica and the interfacial conformation of the peptide. Results indicate that phosphorylation drastically decreases the binding free energy and changes the structure of silica-adsorbed R5 through the introduction of charge and steric repulsion. New mechanistic insights from this work could inform rational design of new biomaterials and biotechnologies.