In many protein kinases, a characteristic conformational change (the "DFG flip") connects catalytically active and inactive conformations. Many kinase inhibitors--including the cancer drug imatinib--selectively target a specific DFG conformation, but the function and mechanism of the flip remain unclear. Using long molecular dynamics simulations of the Abl kinase, we visualized the DFG flip in ...

Deoxyfructosyl glutamine (DFG, referred to elsewhere as dfg) is a naturally occurring Amadori compound found in rotting fruits and vegetables. DFG also is an opine and is found in tumors induced by chrysopine-type strains of Agrobacterium tumefaciens. Such strains catabolize this opine via a pathway coded for by their plasmids. NT1, a derivative of the nopaline-type A. tumefaciens strain C58 la...

Mid-infrared (MIR) ultrashort laser pulses have a wide range of applications in the fields environmental monitoring, medicine, food quality control, strong-field physics, attosecond science, and some other aspects. Recent years seen great developments MIR technologies. Traditional solid-state fiber lasers focus on research short-wavelength region. However, due to limitation gain medium, they st...

During the past 12 years or so, hardly any other field has impacted the art and science of chemical synthesis more profoundly than organocatalysis. The growth, both in academic research and in industrial use, has been breathtaking. Judging by the development of its impact factor, the Beilstein Journal of Organic Chemistry is currently attempting to achieve the same impact within chemistry publi...

Recently, the development of Src/Abl (c-Src/Bcr-Abl tyrosine kinases) dual inhibitors has attracted considerable attention from the research community for treatment of malignancies. In order to explore the different structural features impacting the Src and Abl inhibitory activities of N(9)-arenethenyl purines and to investigate the molecular mechanisms of ligand-receptor interactions, a molecu...

Structural elucidation of the active (DFG-Asp in) and inactive (DFG-Asp out) states of the TAM family of receptor tyrosine kinases is required for future development of TAM inhibitors as drugs. Herein we report a computational study on each of the three TAM members Tyro-3, Axl and Mer. DFG-Asp in and DFG-Asp out homology models of each one were built based on the X-ray structure of c-Met kinase...

Protein tyrosine kinases are crucial to cellular signaling pathways regulating cell growth, proliferation, metabolism, differentiation, and migration. To maintain normal regulation of cellular signal transductions, the activities of tyrosine kinases are also highly regulated. The conformation of a three-residue motif Asp-Phe-Gly (DFG) near the N-terminus of the long "activation" loop covering t...

Kinases can switch between active and inactive conformations of the ATP/Mg(2+) binding motif DFG, which has been explored for the development of type I or type II inhibitors. However, factors modulating DFG conformations remain poorly understood. We chose CDK2 as a model system to study the DFG in-out transition on a target that was thought to have an inaccessible DFG-out conformation. We used ...

BACKGROUND Enucleation in young children often results in retarded orbital growth ipsilaterally. The need for an implant that will naturally grow with the child, like Dermis-fat Graft (DFG), for managing the anophthalmia has been of interest over the years. OBJECTIVE To evaluate the use of DFG as an implant for volume replacement post-enucleation. STUDY DESIGN A prospective non-comparative ...

Abstract The problem of automatically discovering business process models from event logs has been intensely investigated in the past two decades, leading to a wide range approaches that strike various trade-offs between accuracy, model complexity, and execution time. A few studies have suggested accuracy automated discovery can be enhanced by means metaheuristic optimization techniques. Howeve...