Parameterization of Unnatural Amino Acids with Azido and Alkynyl R-Groups for Use in Molecular Simulations
Parameterization of Unnatural Amino Acids with Azido and Alkynyl R-Groups for Use in Molecular Simulations
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DOI：
10.1021/acs.jpca.0c04605
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发表时间：
2020-07-30
影响因子：
2.9
通讯作者：
Knotts，Thomas A.
中科院分区：
文献类型：
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作者：
Smith，Addison K.;Wilkerson，Joshua W.;Knotts，Thomas A.
最近在特定氨基酸位置功能化蛋白质的新方法使用含有叠氮基和炔基的非天然氨基酸。这种能力是前所未有的，可以创建特定位点的蛋白质设备。由于这些装置的高特异性，许多蛋白质结构都是可能的，并且在硅屏幕上显示出预测最佳附着位点位置的希望。因此，有显著的兴趣改进当前的分子动力学（MD）模型，以包括这些线性部分的独特化学。本工作使用力场工具箱获得了含叠氮基和炔基的小分子的键合和非键合CHARMM参数。接下来，通过运行模拟MD分析来测试这些参数的可靠性，以证明模型结构与文献和量子理论中的结构相匹配。最后，蛋白质MD模拟将该参数集与晶体学数据进行比较，以更好地了解非天然氨基酸对蛋白质结构的影响。
Recent new methods to functionalize proteins at specific amino acid locations use unnatural amino acids that contain azido and alkynyl groups. This capability is unprecedented and enables the creation of site-specific protein devices. Because of the high specificity of these devices, many protein configurations are possible and in silico screens have shown promise in predicting optimal attachment site locations. Therefore, there is significant interest in improving current molecular dynamics (MD) models to include the unique chemistries of these linear moieties. This work uses the force field tool kit to obtain the bonded and nonbonded CHARMM parameters for small molecules that contain azido and alkynyl groups. Next, the reliability of these parameters is tested by running simulated MD analysis to prove that the modeled structures match those found in the literature and quantum theory. Finally, the protein MD simulation compares this parameter set with crystallographic data to give a greater understanding of unnatural amino acid influence on the protein structure.