Agnieszka Bronowska's research while affiliated with Newcastle University and other places

... Simulation results show that FAK transiently binds to PIP 2 through electrostatic interactions [72]. Molecular dynamics simulation and fluorescence resonance energy transfer (FRET) experiments both showed that FAK binding to ATP decreases the FRET signal confirming that the PIP 2 binding acts in the reverse direction [73,74]. Phosphatidylinositol 4-phosphate 5-kinase type Iγ (PIP5KIγ) is required for efficient FAK activation and generates PIP 2 locally in FAs by PIP5KIγ. ...

... To complement experiments, molecular-scale simulations have been used to explore vWF in flow. Although valuable results have been obtained from fully atomistic simulations of monomer fragments (e.g., the A2 domain), such simulations cannot probe vWF monomer or multimer behavior (39,40). Besides computational limitations, the complete vWF monomer structure is not yet known. ...

... With this unique combination of properties halogen bonds enable molecular assemblies with manifold conformations. This is particularly interesting for broad applications in the fields of supramolecular chemistry [1][2][3][4] , crystal engineering [5][6][7] , catalysis 8 , and drug design 9,10 . This potential was gradually realized during the last two decades when the nature of the halogen bond was better understood. ...

... GAPDH has an oxidation-sensitive (redox-active) cysteine residue at the enzymatic active site. The cysteine residues are evolutionarily conserved and oxidised by various SH-oxidising reagents and intracellular levels of H 2 O 2 , resulting in many modifications, including disulphide bond formation [14][15][16][17][18][19][20]. However, much of the PK redox regulation mechanism remains unknown. ...

... 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer (pH 7.5, 50 mM) was instilled into the microfluidic channel. Next, 100 µl vWF [48] diluted in HEPES buffer (concentration 10 µg/ml) was instilled and the structures were incubated for 20 min. After rinsing with HEPES buffer, 50 µl of a thrombocyte concentrate (diluted with 450 µl of a DMEM and PSFG mixture down to a concentration of 2.9 × 10 3 thrombocytes/µl) was infused and the structures were incubated for 25 min. ...

... The azapirones (buspirone, gepirone, ipsapirone, tandospirone and zalospirone, Figure 1) have been known to exhibit anxiolytic and antidepressant activities 16 . 1-(2-Pyrimidinyl)piperazinyl (1-PP) pharmacophore widely exists in the azapirones structure and it is an active metabolite of azapirones 17 . The most notable azapirone, buspirone, is a selective 5-HT1A agonist that is used clinically as an antidepressant drug [18][19][20] . ...

... The position of the inhibitor, water molecules, and residues within 4 Å were optimized in AMBER 14 implying the IGB7 implicit solvent model. The gas-phase interaction energies were computed as the energy difference between the energy of the complex and of its constituent parts (i.e., protein, ligand, and bridging water molecules) [34][35][36] at the PM6-D3H4X [37,38] level of theory using MOPAC2016 [39] and Cuby4 [40,41] software. "Free" energies refer to the sums of gas phase energies and solvation free energies. ...

... Evans and Bronowska published a molecular dynamics (MD) study of the catalytic domains of four DNMTs upon SAM binding [55]. In that work, the apo protein, SAM-bound and SAH-bound complexes were studied using crystal structures of DNMT3A, DNMT2 and homology models of DNMT1 and DNMT3B. ...

... Currently, in medicinal chemistry, there is a tendency to search for new psychotropic drugs (antidepressant, anxiolytic, and antipsychotic) by designing compounds with non-selective properties. The rational approaches, in which structural features from selective ligands are combined to produce the designed multiple ligands (DML), claim that parallel modulation of definite multiple biological targets can be beneficial for the treatment of diseases with complex etiology (Krajewski et al., 2001;Morphy, 2012;Roth, Sheffler, & Kroeze, 2004). DML strategy is profitable for psychiatric disorders in view of the facts that complex etiology of mental disorders is controlled by multiple receptor systems or enzymes, which forms an extensive network of connections. ...

... Accordingly, different strategies have been developed to overcome these limitations, such as site-specific tethering [20] or the use of recombinant affinity tags [6,21]. Among them, coiled-coil motifs such as the E5/K5 tandem have received a growing attention for their stability and versatility [22,23]. Accordingly, we have developed such a capture system based on the immobilization of recombinant E5-tagged growth factors onto K5-functionalized supports in an oriented, stable and site-specific manner [8,24]. ...