Essence of Small Molecule-Mediated Control of Hydroxyapatite Growth: Free Energy Calculations of Amino Acid Side Chain Analogues
Essence of Small Molecule-Mediated Control of Hydroxyapatite Growth: Free Energy Calculations of Amino Acid Side Chain Analogues
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小分子介导的羟基磷灰石生长控制的本质：氨基酸侧链类似物的自由能计算
DOI：
10.1021/acs.jpcc.7b12142
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发表时间：
2018-02
影响因子：
3.7
通讯作者：
Sahai Nita
中科院分区：
文献类型：
--
作者：
Xu Zhijun;Wei Qichao;Zhao Weilong;Cui Qiang;Sahai Nita
为了揭示骨生物矿化机制，人们付出了很多努力，通过该机制，羟基磷灰石（HAP）板状晶体的生长在纤维状胶原基质内受到调节。带有大量羧酸盐和磷酸盐氨基酸残基的酸性非胶原酸性蛋白（NCP）是HAP晶体形态的有效调节剂。为了揭示生长调节机制的能量和结构本质，我们在这里进行了先进的分子动力学模拟，以获得酸性和不带电荷的极性氨基酸的侧链类似物（SCA）以及相应的两性离子主链（BB）片段的吸附自由能，并将结果与整个氨基酸分子的结果进行比较。我们观察到，与 (001) 面相比，带负电荷的 SCA（处于两种质子化状态的磷酸丝氨酸，天冬氨酸和谷氨酸）和两性离子 BB 优先结合到 HAP (100) 表面，这与 [100] 是首选生长方向一致。
Much effort has been exerted to unravel the bone biomineralization mechanism by which the growth of plate-shaped crystals of hydroxyapatite (HAP) is regulated within a fibrillar collagen matrix. Acidic noncollagenous acidic proteins (NCPs) bearing a large number of carboxylate and phosphorylate amino acid residues are effective regulators of HAP crystal morphology. To reveal the energetic and structural essence of the growth-regulation mechanism, we performed here advanced molecular dynamics simulations to obtain adsorption free energies of side chain analogues (SCAs) of acidic and uncharged polar amino acids as well as the corresponding zwitterionic backbone (BB) fragment and compared the results to those for the entire amino acid molecule. We observed that negatively charged SCAs (phosphoserine in two protonation states, aspartate and glutamate) and the zwitterionic BB preferentially bind to the HAP (100) surface compared to the (001) face, consistent with [100] being the preferred growth direction for ...