Impact of Glutamate Carboxylation in the Adsorption of the α-1 Domain of Osteocalcin to Hydroxyapatite and Titania.
Impact of Glutamate Carboxylation in the Adsorption of the α-1 Domain of Osteocalcin to Hydroxyapatite and Titania.
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DOI：
10.1039/c9me00158a
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发表时间：
2020-03-01
影响因子：
3.6
通讯作者：
Pfaendtner J
中科院分区：
文献类型：
--
作者：
Alamdari S;Pfaendtner J
一种提出的植入物污染机制归因于非胶原性骨基质蛋白（NCP）非特异性吸附到新植入界面上。为了捕获控制这些NCP识别结构域变化的基本机械力和热力学力，作为γ-羧基谷氨酸（Gla）翻译后修饰和表面化学的函数，我们探测了最常见的NCP骨钙素在矿物和金属氧化物表面上的吸附过程。在这里，我们采用两种增强的采样方法来独立地探测翻译后修饰和肽结构对吸附的影响。首先，在生理pH值下，使用良好回火的代谢动力学来捕获乙酰基和N-甲基酰胺封端的谷氨酸和Gla单氨基酸与结晶羟基磷灰石和二氧化钛模型表面的结合。然后，使用良好回火的集合体中的平行回火代谢动力学（PTMetaD-WTE）来研究骨钙素的α − 1结构域在羟基磷灰石和二氧化钛上的吸附。对骨钙素的α − 1结构域进行了完全脱羧（dOC）和完全羧化（OC）形式的模拟。我们的模拟发现，由于羧化导致的电荷密度增加，在界面处的相互作用增加，并且单个氨基酸对两个表面的吸附更强。有趣的是，Gla在促进α − 1结构域中的紧凑和螺旋结构中的作用导致了两个表面上不同的结合模式，这归因于界面水行为的差异。总的来说，这项工作提供了一个基准，了解机制，驱动吸附含钙矿化蛋白到不同的表面化学。
One proposed mechanism of implant fouling is attributed to the nonspecific adsorption of non-collagenous bone matrix proteins (NCPs) onto a newly implanted interface. With the goal of capturing the fundamental mechanistic and thermodynamic forces that govern changes in these NCP recognition domains as a function of γ-carboxyglutamic acid (Gla) post-translational modification and surface chemistry, we probe the adsorption process of the most commonly occurring NCP, osteocalcin, onto a mineral and metal oxide surface. Here, we apply two enhanced sampling methods to independently probe the effects of post-translational modification and peptide structure on adsorption. First, well-tempered metadynamics was used to capture the binding of acetyl and N-methylamide capped glutamic acid and Gla single amino acids onto crystalline hydroxyapatite and titania model surfaces at physiological pH. Following this, parallel tempering metadynamics in the well-tempered ensemble (PTMetaD-WTE) was used to study adsorption of the α−1 domain of osteocalcin onto hydroxyapatite and titania. Simulations were performed for the α−1 domain of osteocalcin in both its fully decarboxylated (dOC) and fully carboxylated (OC) form. Our simulations find that increased charge density due to carboxylation results in increased interactions at the interface, and stronger adsorption of the single amino acids to both surfaces. Interestingly, the role of Gla in promoting compact and helical structure in the α−1 domain resulted in disparate binding modes at the two surfaces, which is attributed to differences in interfacial water behavior. Overall, this work provides a benchmark for understanding the mechanisms that drive adsorption of Gla-containing mineralizing proteins onto different surface chemistries.
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影响因子：
8.2
作者：
Damiati L;Eales MG;Nobbs AH;Su B;Tsimbouri PM;Salmeron-Sanchez M;Dalby MJ
通讯作者：
Dalby MJ
DOI：
10.1016/j.matbio.2016.01.007
发表时间：
2016-05
期刊：
Matrix biology : journal of the International Society for Matrix Biology
影响因子：
--
作者：
Boskey AL;Villarreal-Ramirez E
通讯作者：
Villarreal-Ramirez E
影响因子：
3.9
作者：
Deighan, Michael;Pfaendtner, Jim
通讯作者：
Pfaendtner, Jim
影响因子：
4.4
作者：
ESSMANN, U;PERERA, L;PEDERSEN, LG
通讯作者：
PEDERSEN, LG
影响因子：
64.8
作者：
Ducy, P;Desbois, C;Karsenty, G
通讯作者：
Karsenty, G