Alves Luiz Anastacio, Ferreira Natiele Carla da Silva, Maricato Victor, Alberto Anael Viana Pinto, Dias Evellyn Araujo, Jose Aguiar Coelho Nt
Laboratory of Cellular Communication, Oswaldo Cruz Institute - Fiocruz, Rio de Janeiro, Brazil.
National Institute of Industrial Property - INPI and Veiga de Almeida University - UVA, Rio de Janeiro, Brazil.
Front Chem. 2022 Jan 20;9:787194. doi: 10.3389/fchem.2021.787194. eCollection 2021.
Despite the increasing number of pharmaceutical companies, university laboratories and funding, less than one percent of initially researched drugs enter the commercial market. In this context, virtual screening (VS) has gained much attention due to several advantages, including timesaving, reduced reagent and consumable costs and the performance of selective analyses regarding the affinity between test molecules and pharmacological targets. Currently, VS is based mainly on algorithms that apply physical and chemistry principles and quantum mechanics to estimate molecule affinities and conformations, among others. Nevertheless, VS has not reached the expected results concerning the improvement of market-approved drugs, comprising less than twenty drugs that have reached this goal to date. In this context, graph neural networks (GNN), a recent deep-learning subtype, may comprise a powerful tool to improve VS results concerning natural products that may be used both simultaneously with standard algorithms or isolated. This review discusses the pros and cons of GNN applied to VS and the future perspectives of this learnable algorithm, which may revolutionize drug discovery if certain obstacles concerning spatial coordinates and adequate datasets, among others, can be overcome.
尽管制药公司、大学实验室的数量不断增加,资金投入也在增加,但最初研发的药物进入商业市场的比例不到1%。在这种背景下,虚拟筛选(VS)因其诸多优势而备受关注,这些优势包括节省时间、降低试剂和耗材成本以及对测试分子与药理学靶点之间的亲和力进行选择性分析。目前,虚拟筛选主要基于应用物理和化学原理以及量子力学来估计分子亲和力和构象等的算法。然而,在改善已获市场批准的药物方面,虚拟筛选尚未达到预期效果,迄今为止达到这一目标的药物不到20种。在这种背景下,图神经网络(GNN)作为一种最新的深度学习子类型,可能成为一种强大的工具,用于改善针对天然产物的虚拟筛选结果,它既可以与标准算法同时使用,也可以单独使用。本文综述了将图神经网络应用于虚拟筛选的优缺点以及这种可学习算法的未来前景,如果能够克服诸如空间坐标和足够数据集等某些障碍,它可能会彻底改变药物发现。