Volume 50, Number 2, April-June 2016
Special issue: Recent Advances in Operations Research in Computational Biology, Bioinformatics and Medicine
|Page(s)||387 - 400|
|Published online||28 March 2016|
Milp-hyperbox classification for structure-based drug design in the discovery of small molecule inhibitors of SIRTUIN6
1 Department of Computational Science
and Engineering, Koc University, 34450
2 Department of Industrial Engineering, Koc University, 34450 Istanbul, Turkey.
3 Department of Molecular Biology and Genetics, Koc University, 34450 Istanbul, Turkey.
4 Department of Chemical and Biological Engineering, Koc University, 34450 Istanbul, Turkey.
Accepted: 21 September 2015
Virtual screening of chemical libraries following experimental assays of drug candidates is a common procedure in structure-based drug discovery. However, virtual screening of chemical libraries with millions of compounds requires a lot of time for computing and data analysis. A priori classification of compounds in the libraries as low- and high-binding free energy sets decreases the number of compounds for virtual screening experiments. This classification also reduces the required computational time and resources. Data analysis is demanding since a compound can be described by more than one thousand attributes that make any data analysis very challenging. In this paper, we use the hyperbox classification method in combination with partial least squares regression to determine the most relevant molecular descriptors of the drug molecules for an efficient classification. The effectiveness of the approach is illustrated on a target protein, SIRT6. The results indicate that the proposed approach outperforms other approaches reported in the literature with 83.55% accuracy using six common molecular descriptors (SC-5, SP-6, SHBd, minHaaCH, maxwHBa, FMF). Additionally, the top 10 hit compounds are determined and reported as the candidate inhibitors of SIRT6 for which no inhibitors have so far been reported in the literature.
Mathematics Subject Classification: 90C11
Key words: Structure-based drug design / SIRT6 / MILP-HB
© EDP Sciences, ROADEF, SMAI 2016
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