Mapping transmembrane residues of proteinase activated receptor 2 (PAR) that influence ligand-modulated calcium signaling.

Proteinase-activated receptor 2 (PAR) is a G protein-coupled receptor involved in metabolism, inflammation, and cancers. It is activated by proteolysis, which exposes a nascent N-terminal sequence that becomes a tethered agonist. Short synthetic peptides corresponding to this sequence also activate PAR, while small organic molecules show promising PAR antagonism.

Helix-constrained nociceptin peptides are potent agonists and antagonists of ORL-1 and nociception.

Nociceptin (orphanin FQ) is a 17-residue neuropeptide hormone with roles in both nociception and analgesia. It is an opioid-like peptide that binds to and activates the G-protein-coupled receptor opioid receptor-like-1 (ORL-1, NOP, orphanin FQ receptor, kappa-type 3 opioid receptor) on central and peripheral nervous tissue, without activating classic delta-, kappa-, or mu-opioid receptors or being inhibited by the classic opioid antagonist naloxone. The three-dimensional structure of ORL-1 was recently published, and the activation mechanism is believed to involve capture by ORL-1 of the high-affinity binding, prohelical C-terminus.

Computational investigation of locked nucleic acid (LNA) nucleotides in the active sites of DNA polymerases by molecular docking simulations.

Aptamers constitute a potential class of therapeutic molecules typically selected from a large pool of oligonucleotides against a specific target. With a scope of developing unique shorter aptamers with very high biostability and affinity, locked nucleic acid (LNA) nucleotides have been investigated as a substrate for various polymerases. Various reports showed that some thermophilic B-family DNA polymerases, particularly KOD and Phusion DNA polymerases, accepted LNA-nucleoside 5'-triphosphates as substrates.

Matching cavities in g protein-coupled receptors to infer ligand-binding sites.

To understand the activity and cross reactivity of ligands and G protein-coupled receptors, we take stock of relevant existing receptor mutation, sequence, and structural data to develop a statistically robust and transparent scoring system. Our method evaluates the viability of binding of any ligand for any GPCR sequence of amino acids. This enabled us to explore the binding repertoire of both receptors and ligands, relying solely on correlations between carefully identified receptor features and without requiring any chemical information about ligands.

Structure aided design of chimeric antibiotics.

The rise of antibiotic resistance is of great clinical concern. One approach to reducing the development of resistance is to co-administer two or more antibiotics with different modes of action. However, it can be difficult to control the distribution and pharmacokinetics of two drugs to ensure both concentrations remain within the range of therapeutic efficacy whilst avoiding adverse effects.