One of the major unsolved problems in bioinformatics is the protein folding problem: given an amino acid sequence, predict the overall three-dimensional structure of the corresponding protein. It has been known since the seminal work of Christian B. Anfinsen in the early seventies that the sequence of a protein encodes its structure, but the exact details of the encoding still remain elusive. Since the protein folding problem is of enormous practical, theoretical and medical importance – and in addition forms a fascinating intellectual challenge – it is often called the holy grail of bioinformatics.Currently, most protein structure prediction methods are based on rather ad hoc approaches. The aim of this project is to develop and implement a statistically rigorous method to predict the structure of proteins, building on various probabilistic models of protein structure developed by the Hamelryck group (see Bibliography). The method will also take the dynamic nature of proteins into account.
Boomsma, W., Mardia, KV., Taylor, CC., Ferkinghoff-Borg, J., Krogh, A. and Hamelryck, T. (2008) A generative, probabilistic model of local protein structure. Proc. Natl. Acad. Sci. USA, 105, 8932-8937
Mardia, KV., Kent, JT., Zhang, Z., Taylor, C., Hamelryck, T. (2012) Mixtures of concentrated multivariate sine distributions with applications to bioinformatics. J. Appl. Stat. 39, 2475-2492.
Boomsma, W., Frellsen, J., Harder, T., Bottaro, S., Johansson, KE., Tian, P., Stovgaard, K., Andreetta, C., Olsson, S., Valentin, J., Antonov, L., Christensen, A., Borg, M., Jensen, J., Lindorff-Larsen, K., Ferkinghoff-Borg, J., Hamelryck, T. (2013) PHAISTOS: A framework for Markov chain Monte Carlo simulation and inference of protein structure. J. Comput. Chem. 34, 1697-705
Hamelryck, T., Mardia, KV., Ferkinghoff-Borg, J., Editors. (2012) Bayesian methods in structural bioinformatics. Book in the Springer series “Statistics for biology and health”, 385 pages, 13 chapters. Springer Verlag, March, 2012
Valentin, J., Andreetta, C., Boomsma, W., Bottaro, S., Ferkinghoff-Borg, J., Frellsen, J., Mardia, KV, Tian, P., Hamelryck, T. (2013) Formulation of probabilistic models of protein structure in atomic detail using the reference ratio method. Proteins. Accepted.
Requirements: Knowledge of statistics, machine learning and programming (C++ or equivalent). Knowledge of biology or biophysics is a plus but not a requirement.
Place of enrollment: Department of Biology, Bioinformatics Center
Supervisor: Assoc. Prof. Thomas Hamelryck
Co-supervisor: Prof. Michael Sørensen from Department of Mathematical Sciences
Apply here: http://dsin.ku.dk/positions/