A/Professor Ashley Buckle
NHMRC Senior Research Fellow
Head, Protein Engineering and Design Lab
OTHER PROGRAM AFFILIATIONS
Cancer , Cardiovascular Disease
Tel: +61 3 9902 9313
We combine x-ray crystallography and biophysics with molecular simulation to study the structure, folding and dynamics of proteins, with a particular focus on the design and engineering of proteins for medical and biotechnological application. Our team is a unique and exciting mix of experimentalists and computational biologists using modeling and simulation to make predictions that can be tested in the lab.
Recent Selected Publications (see PubMed for all):
Direct and indirect mechanisms of KLK4 inhibition revealed by structure and dynamics.
Riley BT, Ilyichova O, Costa MG, Porebski BT, de Veer SJ, Swedberg JE, Kass I, Harris JM, Hoke DE, Buckle AM. Sci Rep. 2016 Oct 21;6:35385. doi: 10.1038/srep35385.
The role of protein dynamics in the evolution of new enzyme function.
Campbell E, Kaltenbach M, Correy GJ, Carr PD, Porebski BT, Livingstone EK, Afriat-Jurnou L, Buckle AM, Weik M, Hollfelder F, Tokuriki N, Jackson CJ. Nature Chem Biol. 2016 Nov;12(11):944-950. doi: 10.1038/nchembio.2175.
Smoothing a rugged protein folding landscape by sequence-based redesign.
Porebski BT, Keleher S, Hollins JJ, Nickson AA, Marijanovic EM, Borg NA, Costa MG, Pearce MA, Dai W, Zhu L, Irving JA, Hoke DE, Kass I, Whisstock JC, Bottomley SP, Webb GI, McGowan S, Buckle AM. Sci Rep. 2016 Sep 26;6:33958. doi: 10.1038/srep33958.
Circumventing the stability-function trade-off in an engineered FN3 domain.
Porebski BT, Conroy PJ, Drinkwater N, Schofield P, Vazquez-Lombardi R, Hunter MR, Hoke DE, Christ D, McGowan S, Buckle AM. Protein Eng Des Sel. 2016 Aug 29.
Cofactor-dependent conformational heterogeneity of GAD65 and its role in autoimmunity and neurotransmitter homeostasis.
Kass I, Hoke DE, Costa MG, Reboul CF, Porebski BT, Cowieson NP, Leh H, Pennacchietti E, McCoey J, Kleifeld O, Borri Voltattorni C, Langley D, Roome B, Mackay IR, Christ D, Perahia D, Buckle M, Paiardini A, De Biase D and Buckle AM. 2014. Proc. Natl. Acad. Sci. USA, 111(25):E2524-9.
Conformational properties of the disease-causing Z variant of α1 antitrypsin revealed by theory and experiment.
Kass I, Knaupp A, Bottomley S and Buckle AM. 2012. Biophys. Journal, 102, 2856-65
Smoothing of five hypothetical energy landscapes by consensus design. Five protein homologues exhibit differences in their energy landscapes, with three containing kinetic traps that present a propensity for misfolding. As the kinetic traps are not conserved across all five homologues, consensus design is capable of smoothing out the energy landscape to eliminate non-conserved features. Reproduced from Porebski and Buckle, Protein Eng Des Sel. 2016 Jul;29(7):245-51