A5101669789- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- RNA and protein synthesis mechanisms
- DNA and Nucleic Acid Chemistry
- Bacteriophages and microbial interactions
- Receptor Mechanisms and Signaling
- Crystallography and molecular interactions
- Computational Drug Discovery Methods
- Legionella and Acanthamoeba research
- Chemical Synthesis and Analysis
- Vibrio bacteria research studies
- RNA modifications and cancer
- Mitochondrial Function and Pathology
- Bacterial biofilms and quorum sensing
- Environmental and Sediment Control
- Monoclonal and Polyclonal Antibodies Research
- Thyroid Disorders and Treatments
- Archaeology and ancient environmental studies
- Genomics and Phylogenetic Studies
- Water Quality and Resources Studies
- ATP Synthase and ATPases Research
- RNA Research and Splicing
- Protein Structure and Dynamics
- Cancer-related molecular mechanisms research
- Synthesis and biological activity
Cardiff University
2020
RF Laboratories (United States)
2019
Case Western Reserve University
2018
MRC Laboratory of Molecular Biology
2008-2016
Depomed (United States)
2011
Menlo School
2011
University of Cape Town
2006-2011
Pennsylvania State University
2008-2009
University of Hawaii System
2008
University of Rochester
2008
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMolecular Dynamics Simulations on Solvated Biomolecular Systems: The Particle Mesh Ewald Method Leads to Stable Trajectories of DNA, RNA, and ProteinsT. E. III Cheatham, J. L. Miller, T. Fox, A. Darden, P. KollmanCite this: Am. Chem. Soc. 1995, 117, 14, 4193–4194Publication Date (Print):April 1, 1995Publication History Published online1 May 2002Published inissue 1 April...
We apply continuum solvent models to investigate the relative stability of various conformational forms for two RNA sequences, GGAC(UUCG)GUCC and GGUG(UGAA)CACC. In first part, we compare alternate hairpin conformations explore reliability these discriminate between different local conformations. A second part looks at hairpin-duplex conversion UUCG sequence, identifying major contributors thermodynamics a much large scale transition. Structures were taken as snapshots from multi-nanosecond...
The β1-adrenoceptor (β1AR) is a G protein-coupled receptor (GPCR) that activated by the endogenous agonists adrenaline and noradrenaline. We have determined structure of an ultra-thermostable β1AR mutant bound to weak partial agonist cyanopindolol 2.1 Å resolution. High-quality crystals (100 μm plates) were grown in lipidic cubic phase without assistance T4 lysozyme or BRIL fusion cytoplasmic loop 3, which commonly employed for GPCR crystallisation. An intramembrane Na+ ion was identified...
Type IV secretion systems (T4SS) are utilized by a wide range of Gram negative bacteria to deliver protein and DNA substrates recipient cells. The best characterized T4SS the type IVA systems, which exhibit extensive similarity Agrobacterium VirB T4SS. In contrast, IVB share almost no sequence homology composed approximately twice as many proteins, remain largely uncharacterized. include Dot/Icm found in pathogens Legionella Coxiella conjugative apparatus IncI plasmids. Here we report first...
A variety of nickel(aryl)(CF3) complexes supported by a chelating bisphosphine were successfully prepared in order to investigate the possibility reductive elimination Ar−CF3. The first structural comparison Ni−CF3 complex with Ni−CH3 is also presented. All new thermally stable and did not produce Ar−CF3 under thermal conditions. Additives had very little effect on eliminations, although water was found afford product 22% yield.
ABSTRACT Legionella pneumophila utilizes a type IV secretion system (T4SS) encoded by 26 dot / icm genes to replicate inside host cells and cause disease. In contrast all other L. dot/icm genes, dotU icmF have homologs in wide variety of gram-negative bacteria, none which possess T4SS. Instead, orthologs are linked locus encoding conserved cluster proteins designated IcmF-associated homologous proteins, has been proposed constitute novel cell surface structure. We show here that is partially...
Introduction: Variants in the intron splicing enhancer (ISE) of 3 GH1 gene are implicated etiology isolated growth hormone deficiency Type 2 (Type II IGHD). Methods: Exome sequencing was performed to screen variants that co-segregated with IGHD an extended family IGHD. The causality candidate variant assessed using bioinformatic tools and previous vitro studies. Results: identified a rare intronic (NM_000515.5, c.291+34 G>A) second XGGG repeat ISE GH1, which occurred de novo mother passed...
We present free energy perturbation calculations on the solvation energies of N-methylated nucleic acid bases adenine, guanine, cytosine, thymine, and uracil. This work demonstrates importance using thermodynamic cycles, a careful study convergence, use both single dual topologies. find that calculated 9-methyladenine 1-methylthymine are close to available experimental data. Additionally, we predict for 9-methylguanine, 1-methylcytosine, 1-methyluracil. The topologies used in these...
Phosphorylation of bacterial ribosomal proteins has been known for decades; however, there is still very limited information available on specific locations the phosphorylation sites in and role they might play protein synthesis. In this study, we have mapped 24 Escherichia coli by tandem mass spectrometry. Detection was achieved either visualization techniques, ProQ staining, antibodies phospho-Ser, Thr, Tyr; or spectrometry equipped with a capability to detect addition loss phosphate...
The high failure rate of drugs in the development phase requires a strategy to reduce risks by generating lead candidates from different chemical classes. We describe new three-dimensional computational approach for evolution, based on multiple pharmacophore hypotheses. Using full conformational models both active and inactive compounds, large number hypotheses are analyzed select set or "ensemble" that, when combined, is most able discriminate between molecules. ensemble hypothesis then...
One of the largest challenges facing structural biologists is to predict structure complex molecules in aqueous solution. In this article we show for first time that Locally Enhanced Sampling can be used conjunction with recently implemented Particle-Mesh-Ewald method address challenge. We present results from studies a small RNA tetraloop system (5'-r[GGACUUCGGUCC]) where combined protocol has allowed our simulations rapidly find experimental starting an alternate location phase space.
Legionella pneumophila is able to survive inside phagocytic cells by an internalization route that bypasses fusion of the nascent phagosome with endocytic pathway allow formation a replicative phagosome. The dot/icm genes, major virulence system L. pneumophila, encode type IVB secretion required for intracellular growth. One Dot protein, DotL, has sequence similarity IV coupling proteins (T4CPs). In other systems, are not viability organism. Here we report first example strain, Lp02, in...
Mammalian mitochondrial ribosomes synthesize 13 proteins that are essential for oxidative phosphorylation. In addition to their role in protein synthesis, some of the ribosomal have acquired functions other cellular processes such as apoptosis. Death-associated 3 (DAP3), also referred S29 (MRP-S29), is a GTP-binding pro-apoptotic located small subunit ribosome. Previous studies shown phosphorylation one most likely regulatory mechanisms DAP3 function apoptosis and may be synthesis; however,...
The chloroform/water partition coefficients have been determined for five N-methylated nucleic acid bases (9-methyladenine, 9-methylguanine, 1-methylcytosine, 1-methythymine, and 1-methyluracil) by calculating the absolute solvation free energies of in chloroform using data water calculated previously Miller Kollman (J. Phys. Chem. 1996, 100, 8587). Thermodynamic perturbation calculations with explicit solvent were used to determine energies. Two separate sets simulations performed differing...
Mitochondria, the powerhouse of eukaryotic cells, have their own translation machinery that is solely responsible for synthesis 13 mitochondrially encoded protein subunits oxidative phosphorylation complexes. Phosphorylation a well-known post-translational modification in regulation many processes mammalian mitochondria including phosphorylation. However, there still very limited knowledge on mitochondrial ribosomal proteins and role(s) ribosome function. In this study, we identified are...
To understand the driving forces of aromatic stacking interactions in water, we have performed conformational searches, molecular dynamics simulations, potential mean force (PMF) and free energy perturbation (FEP) calculations, syntheses, NMR studies on sodium (2,2)-bis(indol-1-yl-methyl)acetate (1), 3-indol-1-yl-2-methyl-propionate (2), 3-indol-1-yl-propionate (3). The searches 1 revealed that isobutyric acid linker allows molecule to adopt tilted T-shaped stacked, off-center face-to-face...
The application of an informative, iterative library design strategy is presented for lead identification and optimization. computational algorithm underlying informative systematically uses data from both active inactive compounds maximizes the information gained subsequent design-synthesis-screening cycles. Retrospective analysis a released dataset 17 550 corresponding cyclin-dependent kinase-2 activities showed that yields significant enrichments efficiently discovers novel chemotypes in...
Abstract Studies on the TSH receptor (TSHR) have numerous practical applications in vitro and vivo. For example human monoclonal autoantibodies (MAbs) to TSHR are useful reagents for diagnostics. Measurement of (TRAbs) is helpful diagnosis management autoimmune thyroid disease. Currently available highly sensitive specific assays measure TRAbs use MAb M22 instead TSH. Furthermore, preparations as World Health Organisation International Standard stimulating antibody calibration measuring...
The crystal structures of the thyroid-stimulating hormone receptor (TSHR) leucine-rich repeat domain (amino acids 22-260; TSHR260) in complex with a stimulating human monoclonal autoantibody (M22TM) and blocking (K1-70™) have been solved. However, attempts to purify crystallise free TSHR260, that is not bound an autoantibody, unsuccessful due poor stability TSHR260. We now describe TSHR260 mutant has stabilised by introduction six mutations (H63C, R112P, D143P, D151E, V169R I253R) form...