The aim of this postdoc project will be to map the structural properties of synthetic compact and folded protein sequences. Today’s biology uses protein that have been assigned to only ~2000 structural families, despite the large variability of their functions and the organisms that they come from. While it has been assumed for long that Nature explored all the possible protein structure space, recent studies (including, but not limited to de novo proteins) suggest otherwise. It seems that new protein structures can be constructed and it remains to be elucidated why the natural protein space is limited in its structural repertoire and whether the evolved protein folds are of any specific advantages to their alternatives.
Ongoing projects in our laboratory study the occurrence of structure/function in random/combinatorial sequence libraries. One of the specific aims is to select for specific proteins with function (using in vivo functional selection systems) and/or structure (using both in vitro and in vivo selection pipelines). These subprojects are yielding first hits of proteins that are being structurally characterized. The aim of the advertised project will be high-throughput structural analyses of protein structures gained in these studies with specific focus on the evolutionary aspects. Strong bioinformatic and computational skills should enable the candidate to model the protein structural information or work with experimental data to produce a library of the selected protein structures. Databases of biological protein families will be used to compare the selected structures with natural protein folds and derive any potential similarities. Bioinformatic analyses will be used to design further modifications to stabilize any new potential folds.
The advertised project will open up a window into artificial protein worlds that will inform us about how easy/hard it is to find novel protein structure outside the evolved biological space. The output of the project should be a collection/database of novel protein structures selected from artificial sequence space and besides its value for the field of protein evolution, it might fuel new strategies of protein design.
Funding and project approval:
Human Frontiers Science Program Research Grant Exploration of the structure/function space of prebiotic to biological proteins 06/2019-05/2022
Primus (Charles University)grant In vivo response to unevolved protein sequences: systematic mapping of fitness landscape 01/2020-12/2022
VW Stiftung grant Ghost in the protein: how do new proteins come about? 1/2021-12/2025
Further grant applications are submitted and in preparation.
Required application materials:
How to submit application materials:
Please send email with the required application materials to dr. Klára Hlouchová: email@example.com, Faculty of Science, Charles University, Prague.
The application deadline is July 23, 2021.
For more information please visit the webpage of the JUNIOR Fund project of the Charles University.