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G-protein coupled receptors (GPCRs) are the largest and most pharmaceutically relevant family of membrane proteins. Here, fully unbiased, enhanced sampling simulations of a constitutively active mutant (CAM) of a class A GPCR, the μ-opioid receptor (μOR), demonstrates repeated transitions between the inactive (IS) and active-like (AS-L) states. The interconversion features typical activation/inactivation patterns involving established conformational rearrangements of conserved residues. By contrast, wild-type μOR remains in IS during the same course of simulation, consistent with the low basal activity of the protein. The simulations point to an important role of residue W2936.48 at the “toggle switch” in the mutation-induced constitutive activation. Such role has been already observed for other CAMs of class A GPCRs. We also find a significantly populated intermediate state, rather similar to IS. Based on the remarkable accord between simulations and experiments, we suggest here that this state, which has escaped so far experimental characterization, might constitute an early step in the activation process of the apo μOR CAM.

This work describes the physicochemical characterization of the fruit pulp oil of Caryocar coriaceum (Wittm), “pequi.” The chemical composition was assessed by GLC, which demonstrated the following fatty acid contents: oleic (55.79%), palmitic (34.18%), heptadecenoic (5.86%), linoleic (1.80%), stearic (1.73%), eicosenoic (0.37%) and palmitoleic (0.27%). The vibrational spectroscopy results were typical of an edible oil, and are in accordance with the high unsaturated fatty acid content. Physical properties such as water content, acidity, peroxide index, saponification index, relative density, viscosity and refraction index are reported for the first time for this species. Pequi fruits have a high nutritional value, and are rich in protein and vitamins. In addition, their composition includes essential fatty acids, which accounts for the popular use of the fruit oil for antioxidant and antiinflammatory activity. There is great interest in extending the use of this natural product by exploiting the combined social, economic and therapeutic values of its derivatives.El presente trabajo describe la caracterización físico-química del aceite de la pulpa de Caryocar coriaceum (Wittm), “pequi”. La composición química fue evaluada por GLC, que mostró el siguiente contenido de ácido graso: oleico (55,79%), palmítico (34,18%), heptadecenoico (5,86%), linoleico (1,80%), esteárico (1,73%), eicosenoico (0,37%) y palmitoleico (0,27%). Los resultados de la espectroscopia vibracional fueron típicos de un aceite comestible, y están en concordancia con el alto contenido de ácido graso insaturado. Las propiedades físicas tales como el contenido de agua, la acidez, índice de peróxido, índice de saponificación, densidad relativa, viscosidad e índice de refracción se presentan por primera vez para esta especie. Los frutos de pequi tienen un alto valor nutricional, y son ricos en proteínas y vitaminas; además su composición incluye ácidos grasos esenciales. El aceite de la fruta tiene un uso popular debido a su actividad antioxidante y antiinflamatoria. Hay un gran interés en extender el uso de este producto natural aprovechando los valores sociales, económicos y terapéuticos de sus derivados.