“Identification of potential ligand-binding pockets is an initial step in receptor-based drug design. While many geometric or energy-based binding-site prediction methods characterize the size and shape of protein cavities, few of them offer an estimate of the pocket’s ability to bind small drug-like molecules. Here, we present a shape-based technique to examine binding-site drugg-ability from the crystal structure Wortmannin in vivo of a given protein target.
The method includes the PocketPicker algorithm to determine putative binding-site volumes for ligand-interaction. Pocket shape descriptors were calculated for both known ligand binding sites and empty pockets and were then subjected to self-organizing map clustering. Descriptors were calculated for structures derived from a database of representative drug-protein complexes with experimentally determined binding affinities to characterize the “”druggable pocketome”". The new method provides a means for selecting drug targets and potential ligand-binding
pockets based on structural considerations and addresses orphan binding sites.”
“Embryonic stem cells (ESCs) – undifferentiated cells originating from preimplantation see more stage embryos – have prolonged self-renewal capacity and are pluripotent. Activation of the canonical Wnt pathway is implicated in maintenance of and exit from the pluripotent state. Recent findings demonstrate that the essential mediator of canonical Wnt signaling, beta-catenin, is dispensable for ESC maintenance; however, its
activation inhibits differentiation through derepression of T cell factor 3 (Tcf3)-bound genes. Wnt agonists are useful in deriving ESCs from recalcitrant mouse strains and the rat and in nuclear reprogramming of somatic stem cells. We discuss recent advances in our understanding of the role of canonical Wnt signaling in the regulation of ESC self-renewal and how its manipulation can improve pluripotent ESC selleck inhibitor derivation and maintenance.”
“Individuals with autism spectrum disorders (ASD) report difficulty integrating simultaneously presented visual and auditory stimuli (larocci & McDonald, 2006), albeit showing enhanced perceptual processing of unisensory stimuli, as well as an enhanced role of perception in higher-order cognitive tasks (Enhanced Perceptual Functioning (EPF) model; Mottron, Dawson, Soulieres, Hubert, & Burack, 2006). Individuals with an ASD also integrate auditory-visual inputs over longer periods of time than matched typically developing (TD) peers (Kwakye, Foss-Feig, Cascio, Stone & Wallace, 2011). To tease apart the dichotomy of both extended multisensory processing and enhanced perceptual processing, we used behavioral and electrophysiological measurements of audio-visual integration among persons with ASD.