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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.01075

Sequence-derived Markers of Drug Targets and Potentially Druggable Human Proteins

Sina Ghadermarzi1, Xingyi Li2,  Min Li2* and  Lukasz Kurgan1*
  • 1Computer Science, Virginia Commonwealth University, United States
  • 2Computer Science and Engineering, Central South University, China

Recent research shows that majority of the druggable human proteome is yet to be annotated and explored. Accurate identification of these unexplored druggable proteins would facilitate development, screening, repurposing and repositioning of drugs, as well as prediction of new drug–protein interactions. We contrast the current drug targets against the datasets of non-druggable and possibly druggable proteins to formulate markers that could be used to identify druggable proteins. We focus on the markers that can be extracted from protein sequences or names/identifiers to ensure that they can be applied across the entire human proteome. These markers quantify key features covered in the past works (topological features of PPIs, cellular functions and subcellular locations) and several novel factors (intrinsic disorder, residue-level conservation, alternative splicing isoforms, domains, and sequence-derived solvent accessibility). We find that the possibly druggable proteins have significantly higher abundance of alternative splicing isoforms, relatively large number of domains, higher degree of centrality in the protein-protein interaction networks and lower numbers of conserved and surface residues, when compared with the non-druggable proteins. We show that the current drug targets and possibly druggable proteins share involvement in the catalytic and signaling functions. However, unlike the drug targets, the possibly druggable proteins participate in the metabolic and biosynthesis processes, are enriched in the intrinsic disorder, interact with proteins and nucleic acids, and are localized across the cell. To sum up, we formulate several markers that can help with finding novel druggable human proteins and provide interesting insights into the cellular functions and subcellular locations of the current drug targets and potentially druggable proteins.

Keywords: Drug Targets, druggability, druggable human proteome, Drug-Protein Interactions, Protein-protein interactions (PPI), intrinsic disorder, human proteome

Received: 30 May 2019; Accepted: 09 Oct 2019.

Copyright: © 2019 Ghadermarzi, Li, Li and Kurgan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Min Li, Central South University, Computer Science and Engineering, Changsha, 130012, Hunan Province, China, limin@mail.csu.edu.cn
Prof. Lukasz Kurgan, Virginia Commonwealth University, Computer Science, Richmond, 23284, Virginia, United States, lkurgan@vcu.edu