Raubenolt Bryan, Blankenberg Daniel
Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Center for Computational Life Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Gigascience. 2024 Jan 2;13. doi: 10.1093/gigascience/giae026.
Viral helicases are promising targets for the development of antiviral therapies. Given their vital function of unwinding double-stranded nucleic acids, inhibiting them blocks the viral replication cycle. Previous studies have elucidated key structural details of these helicases, including the location of substrate binding sites, flexible domains, and the discovery of potential inhibitors. Here we present a series of new Galaxy tools and workflows for performing and analyzing molecular dynamics simulations of viral helicases. We first validate them by demonstrating recapitulation of data from previous simulations of Zika (NS3) and SARS-CoV-2 (NSP13) helicases in apo and complex with inhibitors. We further demonstrate the utility and generalizability of these Galaxy workflows by applying them to new cases, proving their usefulness as a widely accessible method for exploring antiviral activity.
病毒解旋酶是抗病毒疗法开发中很有前景的靶点。鉴于它们具有解开双链核酸的重要功能，抑制它们会阻断病毒复制周期。先前的研究已经阐明了这些解旋酶的关键结构细节，包括底物结合位点的位置、柔性结构域以及潜在抑制剂的发现。在此，我们展示了一系列用于执行和分析病毒解旋酶分子动力学模拟的新Galaxy工具和工作流程。我们首先通过展示重现先前对寨卡病毒（NS3）和解旋酶与抑制剂复合物的模拟数据来对它们进行验证。我们还通过将这些Galaxy工作流程应用于新的案例来进一步证明其效用和通用性，证明它们作为一种广泛可用的探索抗病毒活性方法的有用性。
