Using the DUD-E+ benchmark, we explore the impact of using a single protein pocket or ligand for virtual screening compared with using ensembles of alternative pockets, ligands, and sets thereof. For both structure-based and ligand-based approaches, the precise characterization of the binding site in question had a significant impact on screening p...
Marine sponge holobionts, defined as filter-feeding sponge hosts together with their associated microbiomes, are prolific sources of natural products. The inventory of natural products that have been isolated from marine sponges is extensive. Here, using untargeted mass spectrometry, we demonstrate that sponges harbor a far greater diversity of low...
Tamoxifen is a selective oestrogen receptor modulator (SERM). SERMs act on oestrogen receptors to inhibit oestradiol mediated negative feedback on the hypothalamic-pituitary-gonadal (HPG) axis, thereby upregulating gonadotrophin secretion and release from the pituitary. Hence, Tamoxifen is used to upregulate activation of the HPG axis in the treatm...
Machine learning methods may have the potential to significantly accelerate drug discovery. However, the increasing rate of new methodological approaches being published in the literature raises the fundamental question of how models should be benchmarked and validated. We reanalyze the data generated by a recently published large-scale comparison ...
OBJECTIVE:Almonds are a rich source of fatty acids and antioxidants, and their supplementation is known to significantly modulate serum lipids. The effects of almond on the skin's lipid barrier and the appearance of wrinkles have not yet been elucidated. The aim of this study was to investigate the effects of almond consumption on facial sebum prod...
Copyright © 2019 American Chemical Society. Lysyl oxidase-like 2 (LOXL2) is a secreted enzyme that catalyzes the formation of cross-links in extracellular matrix proteins, namely, collagen and elastin, and is indicated in fibrotic diseases. Herein, we report the identification and subsequent optimization of a series of indole-based fluoroallylamine...
On October 1, 2019, the Society for Medicines Research (SMR) held its first symposium on "Bioelectronic medicines, past, present and future" at the Royal Academy of Engineering in London. The meeting was attended by 145 participants and was supported by Galvani Bioelectronics, IEEE-CAS Society, IEEE-Brain Initiative, BIOS, Heraeus, CorTec and the I...
We introduce a new method for rapid computation of 3D molecular similarity that combines electrostatic field comparison with comparison of molecular surface-shape and directional hydrogen-bonding preferences (called "eSim"). Rather than employing heuristic "colors" or user-defined molecular feature types to represent conformation-dependent molecula...
Fibrosis is a final pathological feature of many chronic diseases, but few interventions are available that specifically target the pathogenesis of fibrosis. The highlights of common cellular and molecular mechanisms of fibrosis facilitate the discovery of effective antifibrotic drugs. The renin-angiotensin system (RAS) plays a central physiologica...
Quantitative Structure-Activity Relationship (QSAR) models are critical in various areas of drug discovery, for example in lead optimisation and virtual screening. Recently, the need for models that are not only predictive but also interpretable has been highlighted. In this paper, a new methodology is proposed to build interpretable QSAR models by...
