Development of enhanced conformational sampling methods to probe the activation landscape of GPCRs.

G protein-coupled receptors (GPCRs) make up the largest superfamily of integral membrane proteins and play critical signal transduction roles in many physiological processes. Developments in molecular biology, biophysical, biochemical, pharmacological, and computational techniques aimed at these important therapeutic targets are beginning to provide unprecedented details on the structural as well as functional basis of their pleiotropic signaling mediated by G proteins, β arrestins, and other transducers. This pleiotropy presents a pharmacological challenge as the same ligand-receptor interaction can cause a therapeutic effect as well as an undesirable on-target side-effect through different downstream pathways.

Understanding G Protein Selectivity of Muscarinic Acetylcholine Receptors Using Computational Methods.

The neurotransmitter molecule acetylcholine is capable of activating five muscarinic acetylcholine receptors, M1 through M5, which belong to the superfamily of G-protein-coupled receptors (GPCRs). These five receptors share high sequence and structure homology; however, the M1, M3, and M5 receptor subtypes signal preferentially through the Gαq/11 subset of G proteins, whereas the M2 and M4 receptor subtypes signal through the Gαi/o subset of G proteins, resulting in very different intracellular signaling cascades and physiological effects. The structural basis for this innate ability of the M1/M3/M5 set of receptors and the highly homologous M2/M4 set of receptors to couple to different G proteins is poorly understood.

The top 100 cited articles published in emergency medicine journals.

Introduction: Our objective was to identify trends and examine the characteristics of the top 100 cited articles in emergency medicine (EM) journals.

Methods: Scopus Library database was queried to determine the citations of the top 100 EM articles. A second database (Google Scholar) was used to gather the following information: number of authors, publication year, journal name, impact factor, country of origin, and article type (original article, review article, conference paper, or editorial).