Structure-based Systems Biology for Analyzing Off-target Binding

By Lei Xie, Li Xie, Philip E. Bourne. 2011

152 citations recorded by the source corpus.

Here off-target binding implies the binding of a small molecule of therapeutic interest to a protein target other than the primary target for which it was intended. Increasingly such off-targeting appears to be the norm rather than the exception, rational drug design notwithstanding, and can lead to detrimental side-effects, or opportunities to reposition a therapeutic agent to treat a different condition. Not surprisingly, there is significant interest in determining a priori what off-targets exist on a proteome-wide scale. Beyond determining putative off-targets is the need to understand the impact of such binding on the complete biological system, with the ultimate goal of being able to predict the phenotypic outcome. While a very ambitious goal, some progress is being made.

Subfields: Computational Theory and Mathematics, Molecular Biology, Radiology, Nuclear Medicine and Imaging

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In Computational Theory and Mathematics

In Molecular Biology

In Radiology, Nuclear Medicine and Imaging

Ruth Nussinov

Citations in the corpus

TANKBind: Trigonometry-Aware Neural NetworKs for Drug-Protein Binding Structure Prediction (2022, background): “Understanding the mechanism-of-actions and off-target effects of drug molecules typically requires analyzing the structures of the related protein-ligand complexes [2, 3], but solving the complex structure experimentally is a an extremely challenging task.”
Structure and dynamics of molecular networks: A novel paradigm of drug discovery: A comprehensive review (2012, methodology): “Consequently both drug–target interaction networks (Section 4.1.3; Xie et al., 2009b; Yang et al., 2010; Azuaje et al., 2011; Xie & Bourne, 2011; Yang et al., 2011; Takarabe et al., 2012; Yu et al., 2012) and drug–disease networks (Hu & Agarwal, 2009) may be used for the prediction of side-effects.”