SEMINAR

Computational protein design: On the cusp between futility and necessity?

Abstract
Synthetic biology relies on molecular building blocks that are simultaneously compatible with as well as orthogonal to existing biological function. Computational protein design offers a possible solution for this task. The focus of this talk will be on the implementation of computational protein design that aims to facilitate creation of new tRNA synthetases for unnatural amino acids. I will present how the approach was applied to this class of proteins and discuss difficulties and pitfalls.

BIOGRAPHY

2014 – present: Professor, Research School of Chemistry, Australian National University
2010-2013: Future Fellow, Research School of Chemistry, Australian National University
2006-2010: Senior lecturer, School of Chemistry and Molecular Biosciences, University of Queensland
2001-2005: DETYA Fellow and Lecturer, Department of Mathematics, University of Queensland
1998-2001: Computational Chemist, Supercomputing Facility, Australian National University
1994-1997: PhD, Laboratory of Physical Chemistry, ETH Zurich Switzerland

Research Fields and Interests:
We use computer algorithm to simulate and rationalise the principles of biomolecular structures. Our work has focussed on new innovative approaches to combine protein structure modelling with experimental techniques. These include, in teamwork with Prof. Nick Dixon (University of Wollongong, UoW) and Prof. Gottfried Otting (ANU), the use of paramagnetic ions and fluoro-amino acids for fast structure-based NMR spectral assignment of proteins. This led to the development of the software programs PLATYPUS, ECHIDNA, POSSUM, NUMBAT and PCS-ROSETTA, and others for mass spectrometry-based protein structure determination. Most recently, we have endeavoured to apply principle knowledge from protein structures to design completely new proteins with novel functions.

Selected Publications:
Porter, J.L., Boon, P.L.S., T.P. Murray, Huber T., Collyer, C.A. and Ollis D.L. (2015) Directed Evolution of New and Improved Enzyme Functions Using an Evolutionary Intermediate and Multi-directional Search. ACS Chem. Biol. 10 611-621.

Chen, W-N., Kuppan, K., Lee, M., Jaudzems, K., Huber, T. and Otting, G.
O-tert-Butyltyrosine, an NMR tag for high-molecular weight systems and measurements of submicromolar ligand binding affinities.
JACS (2015) 137 4581-4586.

Pilla, K.B, Koehler Leman, J., Otting, G. and Huber, T.
Capturing conformational states in proteins using sparse paramagnetic NMR data.
PLoS One (2015) 10 e0127053 (16 pages).

Zhao, Y., Soh, T.S., Chan, K.W.K., Fung, S.S.Y., Swaminathan, K., Lim, S.P., Shi, P-Y., Huber, T., Lescar, J., Luo, D., Vasudevan, S.G.
The Optimal Flexibility of NS5 Methyltransferase-Polymerase Linker Region is Essential for Dengue virus Replication.
J. Virol. (2015) accepted.