Dr Agnieszka Bronowska
Lecturer in Computational Medicinal Chem
- Email: firstname.lastname@example.org
- Telephone: +44 (0) 191 208 3506
- Address: Room 3.35
School of Chemistry
NE1 7RU Newcastle upon Tyne
I am currently a Lecturer in Computational Medicinal Chemistry in the School of Chemistry, Newcastle University. My research interests revolve around thermodynamics-based drug design as a strategy to inhibit ligand-protein, protein-protein, and macromolecule-surface interactions. I am particularly interested in development of allosteric inhibitors. My group is pursuing molecular simulations, quantum chemical calculations, and studies of relationships between structure, dynamics, and biological function of protein-ligand complexes involved in neurodegeneration, chronic inflammation, and cancer, such as IDO1 and other kynurenine pathway enzymes, aryl hydrocarbon receptor (AHR), Hsp90, and mTOR complex. We are also providing molecular simulation support to projects within the School of Chemistry and the Northern Institute for Cancer Research (NICR).
Prior to taking up my appointment in Newcastle I was an Independent BIOMS Research Fellow at the University of Heidelberg, Germany, and earlier a post-doctoral fellow at Heidelberg Institute for Theoretical Studies, where I worked from 2009 in the group of Professor Frauke Graeter, a visiting scientist at the Institute of Biochemistry and Organic Chemistry in Prague, Czech Republic, where I worked with Professor Pavel Hobza, and a post-doctoral researcher at the University of Leeds, in a group of Professor Steve Homans.
1994-1998 - M.Sc. in theoretical chemistry, University of Warsaw, Poland
1998-2001 - Ph.D. in computational medicinal chemistry, University of Warsaw, Poland
My current research projects include, among others:
Kynurenine pathway as a target in treatment strategies for infectious diseases, Alzheimer disease, and for cancer research.
Structure, dynamics, and molecular mechanism of activation of aryl hydrocarbon receptor (AHR) and structure-based development of its antagonists.
Dynamic allostery, allosteric bonds, transient binding sites, and dynamic switches in macromolecular interactions.
“Drugging the undruggable” - probing the dynamics of intrinsically disordered proteins on long (multi-microseconds) time scales in order to develop inhibitors of misfolding and aggregation and potential drugs for neurodegenerative diseases.
Halogen-bonding in molecular recognition. Rational design of halogenated cancer therapeutics and new materials with desired properties.
Repositioning of existing drugs for treatment of chronic and infectious diseases.
I am enthusiastic about mentoring any motivated project students with an interest in molecular simulations (all-atom and coarse-grain molecular dynamics, Monte Carlo simulations, kinetic modelling), molecular docking calculations, virtual screening, protein modelling, and any other aspect of computational biophysics and structure-based drug design.
I am experienced in mentoring students with disabilities (hard of hearing/deaf, autism spectrum disorders, learning difficulties).
- Peralta D, Bronowska AK, Morgan B, Dóka É, VanLaer K, Nagy P, Gräter F, Dick TP. A proton relay enhances H2O2 sensitivity of GAPDH to facilitate metabolic adaptation. Nature Chemical Biology 2015, 11, 156-163.
- Zhou J, Bronowska AK, LeCoq J, Lietha D, Gräter F. Allosteric regulation of focal adhesion kinase by PIP₂ and ATP. Biophysical Journal 2015, 108(3), 698-705.
- Aponte-Santamaría C, Huck V, Posch S, Bronowska AK, Grässle S, Brehm MA, Obser T, Schneppenheim R, Hinterdorfer P, Schneider SW, Baldauf C, Gräter F. Force-sensitive autoinhibition of the von Willebrand factor is mediated by interdomain interactions. Biophysical Journal 2015, 108(9), 2312-2321.
- Zhou J, Aponte-Santamaria C, Sturm S, Bullerjahn JT, Bronowska A, Graeter F. Mechanism of Focal Adhesion Kinase Mechanosensing. PLoS Computational Biology 2015, 11(11), e1004593.
- White SJ, Johnson SD, Sellick MA, Bronowska AK, Stockley PG, Wälti C. The influence of two-dimensional organization on peptide conformation. Angewandte Chemie International Edition 2015, 54(3), 974-978.
- Goñi GM, Epifano C, Boskovic J, Camacho-Artacho M, Zhou J, Bronowska AK, Martín MT, Eck MJ, Kremer L, Gräter F, Gervasio FL, Perez-Moreno M, Lietha D. Phosphatidylinositol 4,5-bisphosphate triggers activation of focal adhesion kinase by inducing clustering and conformational changes. Proceedings of the National Academy of Sciences of the United States of America 2014, 111(31), E3177-E3186.
- Kolár M, Hobza P, Bronowska AK. Plugging the explicit σ-holes in molecular docking. Chem Commun (Camb) 2013, 49(10), 981-983.
- Brahmkshatriya PS, Dobes P, Fanfrlik J, Rezáç J, Paruch K, Bronowska AK, Lepsík M, Hobza P. Quantum mechanical scoring: structural and energetic insights into cyclin-dependent kinase 2 inhibition by pyrazolo[1,5-a]pyrimidines. Curr Comput Aided Drug Des 2013, 1, 118-129.
- White SJ, Morton DW, Cheah BC, Bronowska AK, Davies AG, Stockley PG, Wälti C, Johnson S. On-surface assembly of coiled-coil heterodimers. Langmuir 2012, 28(39), 13877-82.
- Johnson S, Bronowska AK, Chan J, Evans D, Davies AG, Wälti C. Redox-induced conformational change in mercaptoalkanoic acid multilayer films. Langmuir 2012, 28(16), 6632-7.
- Xia F, Bronowska AK, Cheng S, Gräter F. Base-catalyzed peptide hydrolysis is insensitive to mechanical stress. J Phys Chem B 2011, 115(33), 10126-32.
- Bronowska AK. Thermodynamics of Ligand-Protein Interactions: Implications for Molecular Design. In: Juan Carlos Moreno-Pirajan, ed. "Thermodynamics - Interaction Studies - Solids, Liquids and Gases". InTech, 2011.
- Evans DA, Bronowska AK. Implications of fast-time scale dynamics of human DNA/RNA cytosine methyltransferases (DNMTs) for protein function. Theoretical Chemistry Accounts 2010, 125(3), 407-418.
- Fanfrlík J, Bronowska AK, Rezác J, Prenosil O, Konvalinka J, Hobza P. A Reliable Docking/Scoring Scheme Based on the Semiempirical Quantum Mechanical PM6-DH2 Method Accurately Covering Dispersion and H-Bonding: HIV-1 Protease with 22 Ligands. J Phys Chem B 2010, 114(39), 12666-78.
- Syme NR, Dennis C, Bronowska A, Paesen GC, Homans SW. Comparison of Entropic Contributions to Binding in a "Hydrophilic" versus "Hydrophobic" Ligand-Protein Interaction. Journal of the American Chemical Society 2010, 132(25), 8682-8689.
- Merino A, Bronowska AK, Jackson DB, Cahill DJ. Drug profiling: knowing where it hits. Drug Discov Today 2010, 17(18), 749-56.
- Stöckmann H, Bronowska A, Syme NR, Thompson GS, Kalverda AP, Warriner SL, Homans SW. Residual Ligand Entropy in the Binding of p-Substituted Benzenesulfonamide Ligands to Bovine Carbonic Anhydrase II. Journal of the American Chemical Society 2008, 130(37), 12420-12426.
- MacRaild CA, Daranas AH, Bronowska A, Homans SW. Global changes in local protein dynamics reduce the entropic cost of carbohydrate binding in the arabinose-binding protein. Journal of Molecular Biology 2007, 368(3), 822-832.
- Shimokhina N, Bronowska A, Homans SW. Contribution of ligand desolvation to binding thermodynamics in a ligand-protein interaction. Angewandte Chemie: International Edition 2006, 45(38), 6374-6376.
- Barratt E, Bronowska A, Vondrásek J, Cerny J, Bingham R, Phillips S, Homans SW. Thermodynamic penalty arising from burial of a ligand polar group within a hydrophobic pocket of a protein receptor. Journal of Molecular Biology 2006, 362(5), 994-1003.