IEEE Trans Nanobioscience. 2021 Jul;20(3):345-353. doi: 10.1109/TNB.2021.3077710. Epub 2021 Jun 30.
Tubulin is a promising target for designing anti-cancer drugs. Identification of hotspots in multifunctional Tubulin protein provides insights for new drug discovery. Although machine learning techniques have shown significant results in prediction, they fail to identify the hotspots corresponding to a particular biological function. This paper presents a signal processing technique combining resonant recognition model (RRM) and Stockwell Transform (ST) for the identification of hotspots corresponding to a particular functionality. The characteristic frequency (CF) representing a specific biological function is determined using the RRM. Then the spectrum of the protein sequence is computed using ST. The CF is filtered from the ST spectrum using a time-frequency mask. The energy peaks in the filtered sequence represent the hotspots. The hotspots predicted by the proposed method are compared with the experimentally detected binding residues of Tubulin stabilizing drug Taxol and destabilizing drug Colchicine present in the Tubulin protein. Out of the 53 experimentally identified hotspots, 60% are predicted by the proposed method whereas around 20% are predicted by existing machine learning based methods. Additionally, the proposed method predicts some new hot spots, which may be investigated.
微管蛋白是设计抗癌药物的一个有前途的靶点。鉴定多功能微管蛋白中的热点可为新药发现提供深入了解。尽管机器学习技术在预测方面取得了显著的成果,但它们无法识别与特定生物学功能相对应的热点。本文提出了一种结合共振识别模型(RRM)和斯托克韦尔变换(ST)的信号处理技术,用于识别与特定功能相对应的热点。使用 RRM 确定代表特定生物学功能的特征频率(CF)。然后使用 ST 计算蛋白质序列的频谱。使用时频掩模从 ST 谱中滤除 CF。过滤后的序列中的能量峰代表热点。与 Taxol 等微管蛋白稳定药物和 Colchicine 等微管蛋白不稳定药物结合的实验检测到的微管蛋白结合残基进行比较,提出的方法预测了 53 个实验鉴定的热点中的 60%,而现有的基于机器学习的方法预测了约 20%。此外,该方法还预测了一些可能需要研究的新热点。