The depressant β toxin anti-neuroexcitation peptide (ANEP) from the Chinese scorpion Buthus martensii Karsch has analgesic activity by interacting with receptor site 4 of the voltage-gated sodium channels (VGSCs). Here, with molecular dynamics simulations, we examined the binding modes between ANEP and the site 4 of mice sodium channel 1.7 (mNav1.7), a subtype of VGSCs related to peripheral pai...

One of the key ingredients in drug discovery is the derivation of conceptual templates called pharmacophores. A pharmacophore model characterises the physico-chemical properties common to all active molecules, called ligands, bound to a particular protein receptor, together with their relative spatial arrangement. Motivated by this important application, we develop a Bayesian hierarchical model...

Positive cooperativity (auto- and heteroactivation) of drug oxidation, a potential cause of drug interactions, is well established in vitro for cytochrome P450 (P450) 3A4 but to a much lesser extent for other drug-metabolizing P450 isoforms. Using a high throughput fluorescent-based CYP2C9 effector assay, we identified >30 heteroactivators from a set of 1504 structurally diverse compounds. Seve...

Aim: Virus spike glycoprotein of SARS-CoV-2 is a good target for drug discovery. Objective: To examine the potential druggability protein pharmacophore-based discovery and to investigate binding affinity natural products with protein. Methods: Druggable cavities were searched though CavityPlus. A pharmacophore was built used hit identification. Autodock Vina evaluate hits' affinities. 10 chemic...

We predicted the structural basis for pleiotropic signaling of the C-C chemokine type 5 (CCR5) G protein-coupled receptor (GPCR) by predicting the binding of several ligands to the lower-energy conformations of the CCR5 receptor and 11 mutants. For each case, we predicted the ∼ 20 most stable conformations for the receptor along with the binding sites for four anti-HIV ligands. We found that no...

In the era of big data and artificial intelligence, a lot new discoveries have influenced fields antiviral drug design pharmacophore identification.

Alignment or superposition of multiple flexible ligands in 3D is a key step in rational ligand-based drug design, pharmacophore elucidation and 3D QSAR analysis. We have recently introduced Atomic Property Fields methodology, which utilizes continuous Gaussian-based multicomponent potentials to represent the distributions of physico-chemical atomic properties. Calculation of APF pseudo-energy p...

The generation of a pharmacophore model is a challenging process, which often requires the interaction of medicinal chemists. Given a number of ligands for a specific target, the aim is to identify the pharmacophore patterns that are responsible for the biological activities of chemical compounds. A recent study of optimal assignment methods has shown that the assignment of chemical substructur...

Apurinic/apyrimidinic endonuclease 1 (APE1) is an enzyme responsible for the initial step in the base excision repair pathway and is known to be a potential drug target for treating cancers, because its expression is associated with resistance to DNA-damaging anticancer agents. Although several inhibitors already have been identified, the identification of novel kinds of potential inhibitors of...