A candidate ion-retaining state in the inward-facing conformation of sodium/galactose symporter: Clues from atomistic simulations

The recent Vibrio parahaemolyticus sodium/galactose (vSGLT) symporter crystal structure captures the protein in an inward-facing substrate-bound conformation, with the sodium ion placed, by structural alignment, in a site equivalent to the Na2 site of the leucine transporter (LeuT). A recent study, based on molecular dynamics simulations, showed that the sodium ion spontaneously leaves its initial position diffusing outside vSGLT, toward the intracellular space. This suggested that the crystal structure corresponds to an ion-releasing state of the transporter. Here, using metadynamics, we identified a more stable Na+ binding site corresponding to a putative ion-retaining state of the transporter. In addition, our simulations, consistently with mutagenesis studies, highlight the importance of D189 that, without being one of the NA(+)-coordinating residues, regulates its binding/release

Strength of Hydrogen Bond Network Takes Crucial Roles in the Dissociation Process of Inhibitors from the HIV-1 Protease Binding Pocket

To understand the underlying mechanisms of significant differences in dissociation rate constant among different inhibitors for HIV-1 protease, we performed steered molecular dynamics (SMD) simulations to analyze the entire dissociation processes of inhibitors from the binding pocket of protease at atomistic details. We found that the strength of hydrogen bond network between inhibitor and the protease takes crucial roles in the dissociation process. We showed that the hydrogen bond network in the cyclic urea inhibitors AHA001/XK263 is less stable than that of the approved inhibitor ABT538 because of their large differences in the structures of the networks. In the cyclic urea inhibitor bound complex, the hydrogen bonds often distribute at the flap tips and the active site. In contrast, there are additional accessorial hydrogen bonds formed at the lateral sides of the flaps and the active site in the ABT538 bound complex, which take crucial roles in stabilizing the hydrogen bond network. In addition, the water molecule W301 also plays important roles in stabilizing the hydrogen bond network through its flexible movement by acting as a collision buffer and helping the rebinding of hydrogen bonds at the flap tips. Because of its high stability, the hydrogen bond network of ABT538 complex can work together with the hydrophobic clusters to resist the dissociation, resulting in much lower dissociation rate constant than those of cyclic urea inhibitor complexes. This study may provide useful guidelines for design of novel potent inhibitors with optimized interactions

Toward Interconnected Virtual Reality: Opportunities, Challenges, and Enablers

© 1979-2012 IEEE. Just recently, the concept of augmented and virtual reality (AR/VR) over wireless has taken the entire 5G ecosystem by storm, spurring an unprecedented interest from academia, industry, and others. However, the success of an immersive VR experience hinges on solving a plethora of grand challenges cutting across multiple disciplines. This article underscores the importance of VR technology as a disruptive use case of 5G (and beyond) harnessing the latest development of storage/ memory, fog/edge computing, computer vision, artificial intelligence, and others. In particular, the main requirements of wireless interconnected VR are described followed by a selection of key enablers; then research avenues and their underlying grand challenges are presented. Furthermore, we examine three VR case studies and provide numerical results under various storage, computing, and network configurations. Finally, this article exposes the limitations of current networks and makes the case for more theory, and innovations to spearhead VR for the masses

Responsibility, thought-action fusion, and thought suppression in Turkish patients with obsessive-compulsive disorder

Although an inflated sense of responsibility, thought-action fusion, and thought suppression are influential factors in cognitive models of obsessive-compulsive disorder (OCD), their impact on OCD has generally been demonstrated in samples from Western countries. The aim of the present study is to evaluate these cognitive factors in Turkish patients with OCD, other anxiety disorders, and community controls. Group comparisons showed that responsibility based on self-dangerousness and thought suppression significantly distinguished OCD patients from patients with other anxiety disorders and controls. Moreover, correlation and discriminant function analyses indicated that thought-action fusion in morality and likelihood was also associated with OCD symptoms. The present findings provide support for the international validity and specificity of cognitive factors and model for OCD. (C) 2008 Wiley Periodicals, Inc