In silico identification of novel G protein coupled receptors

G-protein coupled receptors (GPCRs) are a superfamily of membrane integral proteins responsible for a large number of physiological functions. Approximately 50% of marketed drugs are targeted toward a GPCR. Despite showing a high degree of structural homology, there is a large variance in sequence within the GPCR superfamily which has lead to difficulties in identifying and classifying potential new GPCR proteins. Here the various computational techniques that can be used to characterize a novel GPCR protein are discussed, including both alignment-based and alignment-free approaches. In addition, the application of homology modeling to building the three-dimensional structures of GPCRs is described.

Synthesis of arbitrary group delay responses with all-pass optical cavities structures

We propose a systematic method for the synthesis of arbitrary group delay responses by using all-pass structures of coupled optical cavities. Optimum structure parameters design, in terms of filter order and accuracy, are obtained.

Synthesis of arbitrary group delay responses with all-pass optical cavities structures

We propose a systematic method for the synthesis of arbitrary group delay responses by using allpass structures of coupled optical cavities. Optimum structure parameters design, in terms of filter order and accuracy, are obtained. © 2012 OSA.

Discrete solitons in coupled active lasing cavities

We examine the existence and stability of discrete spatial solitons in coupled nonlinear lasing cavities (waveguide resonators), addressing the case of active defocusing media, where the gain exceeds damping in the low-amplitude limit. A new family of stable localized structures is found: these are bright and gray cavity solitons representing the connections between homogeneous and inhomogeneous states. Solitons of this type can be controlled by discrete diffraction and are stable when the bistability of homogenous states is absent. © 2012 Optical Society of America.

Structural basis for receptor activity-modifying protein-dependent selective peptide recognition by a G protein-coupled receptor

Association of receptor activity-modifying proteins (RAMP1-3) with the G protein-coupled receptor (GPCR) calcitonin receptor-like receptor (CLR) enables selective recognition of the peptides calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) that have diverse functions in the cardiovascular and lymphatic systems. How peptides selectively bind GPCR:RAMP complexes is unknown. We report crystal structures of CGRP analog-bound CLR:RAMP1 and AM-bound CLR:RAMP2 extracellular domain heterodimers at 2.5 and 1.8 Å resolutions, respectively. The peptides similarly occupy a shared binding site on CLR with conformations characterized by a β-turn structure near their C termini rather than the α-helical structure common to peptides that bind related GPCRs. The RAMPs augment the binding site with distinct contacts to the variable C-terminal peptide residues and elicit subtly different CLR conformations. The structures and accompanying pharmacology data reveal how a class of accessory membrane proteins modulate ligand binding of a GPCR and may inform drug development targeting CLR:RAMP complexes.

Full-vectorial modeling of femtosecond pulses for laser inscription of photonic structures

During the last decade, microfabrication of photonic devices by means of intense femtosecond (fs) laser pulses has emerged as a novel technology. A common requirement for the production of these devices is that the refractive index modification pitch size should be smaller than the inscribing wavelength. This can be achieved by making use of the nonlinear propagation of intense fs laser pulses. Nonlinear propagation of intense fs laser pulses is an extremely complicated phenomenon featuring complex multiscale spatiotemporal dynamics of the laser pulses. We have utilized a principal approach based on finite difference time domain (FDTD) modeling of the full set of Maxwell's equations coupled to the conventional Drude model for generated plasma. Nonlinear effects are included, such as self-phase modulation and multiphoton absorption. Such an approach resolves most problems related to the inscription of subwavelength structures, when the paraxial approximation is not applicable to correctly describe the creation of and scattering on the structures. In a representative simulation of the inscription process, the signature of degenerate four wave mixing has been found. © 2012 Optical Society of America.

Fabrication of surface nanoscale axial photonics structures with a femtosecond laser

Surface nanoscale axial photonics (SNAP) structures are fabricated with a femtosecond laser for the first time, to the best of our knowledge. The inscriptions introduced by the laser pressurize the fiber and cause its nanoscale effective radius variation. We demonstrate the subangstrom precise fabrication of individual and coupled SNAP microresonators having the effective radius variation of several nanometers. Our results pave the way to a novel ultraprecise SNAP fabrication technology based on the femtosecond laser inscription.