Institute of Theoretical Chemistry, College of Chemistry, Jilin University, Changchun, 130023, China.
Institute of Theoretical Chemistry, College of Chemistry, Jilin University, Changchun, 130023, China; Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun, 130023, China.
Comput Biol Med. 2022 Jun;145:105412. doi: 10.1016/j.compbiomed.2022.105412. Epub 2022 Mar 17.
NS1B protein plays an important role in countering host antiviral defense and virulence of influenza virus B, considered as the promising target. The first experimental structure of the NS1B protein has recently been determined, was able to bind to double-stranded RNA (dsRNA). However, few studies attempt to investigate the RNA-binding mechanism of the NS1B. In this study, we provide our understanding of the structure-function relationship, dynamics and RNA-binding mechanism of the NS1B protein by performing molecular dynamics simulations combined and MM-GBSA calculations on the NS1B-dsRNA complex. 12 key residues are identified for RNA-binding by forming hydrogen bonds with the. Our results also demonstrate that mutations (R156A, K160A, R208A and K221A) can cause the local structure changes of NS1B CTD and the hydrogen bonds between NS1B CTD and RNA disappearance, which may be the main reasons for the decrease in RNA-binding affinity. These results mentioned will help us understanding the RNA-binding mechanism and could provide some medicinal chemistry insights chances for rational drug design targeting NS1B protein.
NS1B 蛋白在抵御宿主抗病毒防御和 B 型流感病毒的毒力方面发挥着重要作用，被认为是有前途的靶标。最近已经确定了 NS1B 蛋白的第一个实验结构，它能够结合双链 RNA(dsRNA)。然而，很少有研究试图探究 NS1B 的 RNA 结合机制。在这项研究中，我们通过对 NS1B-dsRNA 复合物进行分子动力学模拟和 MM-GBSA 计算，提供了对 NS1B 蛋白的结构-功能关系、动力学和 RNA 结合机制的理解。通过与. 形成氢键，我们鉴定出 12 个关键残基用于 RNA 结合。我们的结果还表明，突变（R156A、K160A、R208A 和 K221A）可能导致 NS1B CTD 的局部结构变化和 NS1B CTD 与 RNA 之间氢键的消失，这可能是 RNA 结合亲和力下降的主要原因。这些结果将有助于我们理解 RNA 结合机制，并为针对 NS1B 蛋白的合理药物设计提供一些药物化学见解。
