| 邓培渊.化学通报,2019,82(12):1110-1114. |
| 吲哚胺2,3-双加氧化酶I与抑制剂INCB024360 作用的分子动力学研究 |
| Molecular Dynamics Study on Interactions between Indoleamine 2,3-dioxygenase I and INCB024360 |
| 投稿时间：2019-05-31 修订日期：2019-09-11 |
| DOI： |
| 中文关键词: 吲哚胺2,3-双加氧化酶I INCB024360 分子对接 分子动力学 丙氨酸突变扫描 |
| 英文关键词:Indoleamine 2,3-dioxygenase I INCB024360 Molecular docking Molecular dynamics Alanine scanning mutagenesis |
| 基金项目:河南省高校重点科研项目（20A180032） |
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| 中文摘要: |
| INCB024360是进入临床试验的吲哚胺2,3-双加氧化酶I（IDO1）抑制剂之一，但其结合机理尚不明晰。本文运用分子对接、分子动力学、自由能计算等方法研究了IDO1和INCB024360的结合模式,结果表明：IDO1和INCB024360的复合物形成了6个氢键，结合自由能为-70.82 kJ/mol，静电作用力是主要驱动力，极性溶剂化能是主要抑制力；丙氨酸突变扫描发现Ser263和Glu171是两者结合的关键氨基酸，ΔΔGbind值分别为15.35 kJ/mol和54.39 kJ/mol。这些数据为阐明IDO1和INCB02436结合的分子机制提供理论参考。 |
| 英文摘要: |
| INCB024360 is an Indoleamine 2,3-dioxygenase I inhibitors that has entered clinical trial,but
the binding mechanism is still obscure.In this study,the binding pattern of IDO1and INCB024360 was investigated using molecular docking,molecular dynamics.binding free energy calculation methods and alanine scanning mutagenesis.The results showed that six hydrogen bonds are formed in the complex, the binding free energy is -70.82 kJ/mol, and the electrostatic force is main driving forces, the polar solvation energy is main resistance force; Moreover, the alanine scanning mutagenesis experiment revealed that Ser263 and Glu171 are the key residues for the combination and the ΔΔGbind values are 15.35 kJ/mol and 54.39 kJ/mol, respectively. The results presented herein provide an important basis for elucidating the molecular mechanism of binding between IDO1 and INCB024360. |
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