Virtual screening applications in short-chain dehydrogenase/reductase research

Abstract

Several members of the short-chain dehydrogenase/reductase (SDR) enzyme family play fundamental roles in adrenal and gonadal steroidogenesis as well as in the metabolism of steroids, oxysterols, bile acids, and retinoids in peripheral tissues, thereby controlling the local activation of their cognate receptors. Some of these SDRs are considered as promising therapeutic targets, for example to treat estrogen-/androgen-dependent and corticosteroid-related diseases, whereas others are considered as anti-targets as their inhibition may lead to disturbances of endocrine functions, thereby contributing to the development and progression of diseases. Nevertheless, the physiological functions of about half of all SDR members are still unknown. In this respect, in silico tools are highly valuable in drug discovery for lead molecule identification, in toxicology screenings to facilitate the identification of hazardous chemicals, and in fundamental research for substrate identification and enzyme characterization. Regarding SDRs, computational methods have been employed for a variety of applications including drug discovery, enzyme characterization and substrate identification, as well as identification of potential endocrine disrupting chemicals (EDC). This review provides an overview of the efforts undertaken in the field of virtual screening supported identification of bioactive molecules in SDR research. In addition, it presents an outlook and addresses the opportunities and limitations of computational modeling and in vitro validation methods.

Molecular Mechanism Study on Stereo-Selectivity of α or β Hydroxysteroid Dehydrogenases

“…Consisted of more than 163,120 members [21], SDR enzymes are found in different classes of oxidoreductases, isomerases, and lyases [21,22], with multiple functions such as carbonyl-alcohol oxidoreduction, steroid isomerase, enoyl-CoA reduction, decarboxylase, dehalogenase, dehydratase, C=N reduction and epimerase [22][23][24], covering broad substrates such as sugars, steroids, retinoids, lipids, polyols, prostaglandins and androstenedione [24,25]. SDRs could be further classified into six types at least according to their sequence differences, i.e., "Classical," "Extended," "Atypical," "Intermediate," "Divergent," "Complex" and some members "Unassigned" (Table 1) [21,22,26].…”

Structure-based drug repurposing against COVID-19 and emerging infectious diseases: methods, resources and discoveries

“…From among the introduced approaches, drug repurposing (DR) methods, which seek the hidden benefits of the existing drugs in treating different diseases, have produced promising outcomes. Given the capabilities of the computational approaches in reducing the spent time and cost of the drug discovery projects [ 4 ], many studies have been conducted to identify the candidate medicines for treating COVID-19. In this review, based on the utilized computational DR methods, the studies (at the time of conducting this review) have been divided into four classes, including (i) machine learning (ML), (ii) network-based (NB), (iii) structure-based DR (SBDR) and (iv) hybrid approaches.…”

With Chitosan and PLGA as the Delivery Vehicle, Toxoplasma gondii Oxidoreductase-Based DNA Vaccines Decrease Parasite Burdens in Mice

“…However, these vaccine targets cannot fully protect against the virulent challenge, and a suitable vaccine is still unavailable (20)(21)(22). The short-chain dehydrogenases/reductases family (SDR family) is a large family of enzymes in eukaryotes and a potential vaccine target (23), which is involved in the synthesis of molecules, including lipids, vitamins, drugs, and carbohydrates (24). A 368-amino acid protein encoded as "oxidoreductase" from the T. gondii SDR family in the Uniprot database (https://www.uniprot.org/) aroused our particular attention.…”