We have open positions for Ph.D. candidates and a Post-doctoral fellow interested in molecular simulations and structural bioinformatics available. The deadline for the application is April 10, 2018.
Dvorak P, Bednar D, Vanacek P, Balek L, Eiselleova L, Stepankova V, Sebestova E, Kunova Bosakova M, Konecna Z, Mazurenko S, Kunka A, Vanova T, Zoufalova K, Chaloupkova R, Brezovsky J, Krejci P, Prokop Z, Dvorak P, Damborsky J, 2018: Computer-Assisted Engineering of Hyperstable Fibroblast Growth Factor 2. Biotechnology and Bioengineering (just accepted): doi: 10.1002/bit.26531. full text
Fibroblast growth factors (FGFs) serve numerous regulatory functions in complex organisms, and their corresponding therapeutic potential is of growing interest to academics and industrial researchers alike. However, applications of these proteins are limited due to their low stability. Here we tackle this problem using a generalizable computer-assisted protein engineering strategy to create a unique modified FGF2 with nine mutations displaying unprecedented stability and uncompromised biological function. The data from the characterization of stabilized FGF2 showed a remarkable prediction potential of in silico methods and provided insight into the unfolding mechanism of the protein. The molecule holds a considerable promise for stem cell research and medical or pharmaceutical applications.
We have been awarded an OPUS grant from NCN to deliver new approaches for analysis of ligand transport pathways in proteins. The grant will provide funding for notable expansion of our team in the coming three years.
Brezovsky J, Kozlikova B, Damborsky J, 2018: Computational Analysis of Protein Tunnels and Channels. In: Bornscheuer U., Höhne M. (eds) Protein Engineering. Methods in Molecular Biology, vol 1685. Humana Press, New York, NY, pp. 25-42. full text
Protein tunnels connecting the functional buried cavities with bulk solvent and protein channels, enabling the transport through biological membranes, represent the structural features that govern the exchange rates of ligands, ions, and water solvent. Tunnels and channels are present in a vast number of known proteins and provide control over their function. Modification of these structural features by protein engineering frequently provides proteins with improved properties. Here we present a detailed computational protocol employing the CAVER software that is applicable for: (1) the analysis of tunnels and channels in protein structures, and (2) the selection of hot-spot residues in tunnels or channels that can be mutagenized for improved activity, specificity, enantioselectivity, or stability.