ASIAN JOURNAL OF PHYSICS

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Water is an important component in biological systems mediating the interactions of macromolecules with various partners. Water molecules accommodated in binding sites of proteins are of particular importance for drug design. Taking water molecules into account in computational approaches to drug design, however, is an extremely challenging task, especially for a large number of ligands usually used for structure-based virtual screening. We previously developed the approach AMMOS to improve the quality of protein-ligand interaction predictions for in silico screening by using molecular mechanics optimization of docked protein-ligand complexes. In this study, we included explicit water molecules mediating protein-ligand interactions in AMMOS molecular mechanics optimization. The impact of considering water molecules in the protein binding site during the minimization on prediction of the ligand binding modes and binding energies was assessed and reported here.© Anita Publications. All rights reserved.

Keywords: AMMOS, post-docking optimization, binding site, protein flexibility, protein-ligand interactions, water molecules

Total Refs : 36

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Asian Journal of Physics                                                                                                        Vol. 23, No 5 (2014) 757-775

Computational Modeling of Disease Related Missense Mutations in Recently Crystalized Human

G-Protein Coupled Receptors

Justin R Bartanus^1,2, Ben T Nguyen^1,3, Courtney A Balcome¹, Christopher A Henry¹, and Ekaterina I Michonova-Alexova^1*

²Presently a PhD student at Baylor College of Medicine, Houston, TX 77030, USA

³Presently a PhD student at the University of Memphis Graduate School, Memphis, TN 38152, USA Erskine College          
2 Washington Street, Due West, South Carolina 29639-0338, USA

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Electric fields are present in all developing and regenerating animal tissues. During recent years, there has been growing research on the response of cells to the endogenous and exogenously applied electric field. This review discusses the role of endogenous and applied (exogenous) electric field mainly in stimulating tissue regeneration and in cancer treatment by describing: 1) the historical context of bioelectricity, 2) the fundamental principles of cell and tissue response to electric fields, 3) the cellular mechanisms for the effects of low and high electricfields on cell behavior, and 4) the perspectives of using new techniques and approaches for electric field application in tissue regeneration and cancer treatment. © Anita Publications. All rights reserved.

Total Refs : 121

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It is now well established that mitochondrial dysfunction contributes to a variety of disorders ranging from type 2 diabetes, tissue inflammation, cardiac ischemia and cancer¹. For cardiac malfunction, the mechanism of mitochondrial damage has been linked to the dysregulation of cellular ion metabolism followed by intracellular calcium accumulation. Thereby ion dynamics regulation and energetics of cardiac cells under physiological and pathological conditions will provide important insights about the underlying processes. Hypoxic signaling modulates oxidative phosphorylation pathways which in turn leads to energy depletion, accumulation of cytotoxic mediators and cellular apoptosis². Previously it has been demonstrated that complexes III and IV are predominantly affected by reperfusion injury. Recent studies have postulated that under oxygen limiting conditions mitochondria produce NO indicating significant crosstalk between reactive oxygen species (ROS) and reactive nitrogen species (RNS)³.

                In this work we couple the basic building blocks of mitochondrial complexes important for oxidative mechanisms to the key functional units of the two compartment ROS and RNS pathways. In the reduced model we first identify the critically important players which govern the coordination and connectivity of the constituents based on our analysis of a set of hypoxic genes and proteins. That information is utilized to construct a novel mathematical method to transform the signaling network into a coupled system of differential equations (ODE) and also qualitatively analyzed using a binary logic circuit design using logic gates, latches and flip flops⁴. The states denote regulatory activation and inhibition. The evolution of the states is modelled with discrete time models as finite state machines. Evolution of hypoxia in the ODE system is modulated by the peroxide and NO cross-talk mechanisms. The circuit model generates a complementary qualitative information and the models for ionic species is constructed as purely Boolean gates and integrated into the layout of the signaling cascade by feedback loops. Cellular responses are modulated from the interference of the circuit components. In the next stage the leakage in the circuitry is attributed to proton leakage which is propagated in pathway modulating ROS. The stuck open fault mechanism is mapped to ROS homeostasis in the hypoxia-induced mitochondrial autophagy. From a general perspective this study has a promise to become alternative viable model to generate design rules for biochemical pathways which may readily be amenable to very large scale integration (VLSI) process simulation.© Anita Publications. All rights reserved.

Total Refs : 37

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A control experiment is performed to study diffraction of the light from three species of fireflies: one Indian species Luciola praeusta and two Japanese species Luciola cruciata and Luciola lateralis. The firefly emits stable, continuous light a few minutes after it is made to inhale vapors of ethyl acetate. The diffraction pattern produced by a plane diffraction grating of this light shows that the central principal maximum is predominantly yellow. From the first order principal maximum onwards, green and red colored bands appear. With increasing orders, these bands become broader which appear to suppress the yellow band. This result suggests that the intense yellow region, as a matter of fact, is very narrow, and the firefly most probably emits coherent yellow-colored light.© Anita Publications. All rights reserved.

Total Refs : 20