Computational and experimental design of protein function

The aim of this project is to use and improve computational design methodologies for the reliable construction of novel function such as catalytic activities in various protein scaffolds. Rational design is a stringent test of our understanding of biological mechanisms. And in the long run we want to be able to construct proteins with additional features for medical and industrial applications.

At the moment we are applying existing programs to well-studied reaction mechanisms in order to test their applicability. And we are working on the development of additional computational tools. An important part of this work includes the experimental test of theoretical design solutions in the lab. We are also pursuing structural studies on designed ligand-binding proteins to validate predictions in molecular detail.

Selected References:

Malisi, C., Schumann, M., Toussaint, N.C., Kageyama, J., Kohlbacher, O. & Höcker, B. (2012) Binding pocket optimization by computational protein design. PLoS One, 7(12):e52505. [PubMed].

Schreier, B., Stumpp, C., Wiesner, S. & Höcker, B. (2009) Computational design of ligand binding is not a solved problem. Proc Natl Acad Sci U S A 106, 18491-6. [PubMed]

Malisi, C., Kohlbacher, O. & Höcker, B. (2009) Automated scaffold selection for enzyme design. Proteins 77, 74-83. [PubMed]

Claren, J., Malisi, C., Höcker, B. & Sterner, R. (2009) Establishing wild-type levels of catalytic activity on natural and artificial (βα)8-barrel protein scaffolds. Proc Natl Acad Sci U S A 106, 3704-9. [PubMed]