深度学习用于区分SARS-CoV-2尖峰-ACE2分子动力学模拟中的非微不足道的构造变化
Lucas Moraes Dos Santos1, José Gutembergue de Mendonça2, Yan Jerônimo Gomes Lobo3
1Department of Computer Science, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. lucas.santos@dcc.ufmg.br.
Scientific reports
|September 30, 2024
概括
深度学习模型使用分子动力学模拟预测了影响尖端蛋白结合亲和力和免疫性SARS-CoV-2突变. 这种方法有效地识别出可能更具传染性和免疫逃避性的变种.
科学领域:
- 计算生物学和病毒学
- 结构生物学中的机器学习
背景情况:
- 分子动力学 (MD) 模拟产生了庞大的,高维的数据,为分析带来了计算挑战.
- 深度学习的进步为了解MD轨迹的结构变化提供了新的方法,包括突变效应.
研究的目的:
- 为了模拟SARS-CoV-2尖端蛋白-ACE2受体结合域 (RBD) 轨迹,使用间残留距离地图.
- 采用深层卷积神经网络来预测点突变对病毒感染性和免疫性的功能影响.
主要方法:
- 模拟SARS-CoV-2尖端蛋白-ACE2 RBD的MD模拟轨迹作为间残留距离地图.
- 利用深层卷积神经网络来预测蛋白质-ACE2结合和免疫性上的突变效应.
- 分析MD轨迹和中心体,使用2D-RMSD分析,集群和深度学习.
主要成果:
- 该模型成功预测了突变,增加了对人类受体的尖端蛋白亲和力,并降低了免疫性 (精度=0.718,回忆=0.800,AUC=0.800).
- 在平均西格形概率和结合自由能量 (BFE) 变化之间发现了强烈的正相关性 (r=0.776).
- 2D-RMSD分析确定了受体结合基因 (RBM) 中的波动区域,特别是与免疫逃避相关的[公式:参见文本]循环.
结论:
- 该方法提供了一种有效的替代方法,用于识别潜在的SARS-CoV-2菌株,其感染性增加和免疫逃避.
- 该方法利用MD轨迹组合和深度学习来识别突变类型的构造模式,有助于早期发现变异.
- 这项工作加速了针对不断发展的SARS-CoV-2变种和未来的流行病威胁的治疗方法和疫苗的设计.
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