Targeting Epigenetic Regulators Using Machine Learning: Potential Sirtuin 2 Inhibitors

Author:

Kessler Andrew1,Kouznetsova Valentina L.23,Tsigelny Igor F.234

Affiliation:

1. REHS program, San Diego Supercomputer Center, UC San Diego, California, USA

2. San Diego Supercomputer Center, UC San Diego, California, USA

3. BiAna, San Diego, California, USA

4. Department of Neurosciences, UC San Diego, California, USA

Abstract

Sirtuin 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase that has been identified as a target for many diseases, including Parkinson’s disease (PD) and leukemia. Using 234 SIRT2 inhibitors from the ZINC15 database, we generated molecular descriptors with PaDEL and constructed a machine-learning (ML) model for the binary classification of SIRT2 inhibitors. To predict compounds with novel inhibitory mechanisms, we then applied the model on the ZINC15/FDA subset, yielding 107 potential SIRT2 inhibitors. For validation of these substances, we employed the binding analysis software AutoDock Vina to perform virtual screening, with which 43 compounds were considered best inhibitors at the [Formula: see text][Formula: see text]kcal/mol binding affinity threshold. Our results demonstrate the potential of ligand-based (LB) ML techniques in conjunction with receptor-based virtual screening (RBVS) to facilitate the drug discovery or repurposing.

Publisher

World Scientific Pub Co Pte Ltd

Subject

Computational Theory and Mathematics,Physical and Theoretical Chemistry,Computer Science Applications

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