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Computer-assisted engineering of hyperstable fibroblast growth factor 2

P. Dvorak, D. Bednar, P. Vanacek, L. Balek, L. Eiselleova, V. Stepankova, E. Sebestova, M. Kunova Bosakova, Z. Konecna, S. Mazurenko, A. Kunka, T. Vanova, K. Zoufalova, R. Chaloupkova, J. Brezovsky, P. Krejci, Z. Prokop, P. Dvorak, J. Damborsky,

. 2018 ; 115 (4) : 850-862. [pub] 20180124

Language English Country United States

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc19035456

Grant support
NV15-33232A MZ0 CEP Register

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.

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$a Computer-assisted engineering of hyperstable fibroblast growth factor 2 / $c P. Dvorak, D. Bednar, P. Vanacek, L. Balek, L. Eiselleova, V. Stepankova, E. Sebestova, M. Kunova Bosakova, Z. Konecna, S. Mazurenko, A. Kunka, T. Vanova, K. Zoufalova, R. Chaloupkova, J. Brezovsky, P. Krejci, Z. Prokop, P. Dvorak, J. Damborsky,
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$a 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.
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$a Bednar, David $u Faculty of Science, Department of Experimental Biology, Loschmidt Laboratories, Centre for Toxic Compounds in the Environment RECETOX, Masaryk University, Brno, Czech Republic. Faculty of Science, Department of Experimental Biology, Masaryk University, Brno, Czech Republic.
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$a Vanacek, Pavel $u Faculty of Science, Department of Experimental Biology, Loschmidt Laboratories, Centre for Toxic Compounds in the Environment RECETOX, Masaryk University, Brno, Czech Republic. Faculty of Science, Department of Experimental Biology, Masaryk University, Brno, Czech Republic.
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$a Balek, Lukas $u Faculty of Medicine, Department of Biology, Masaryk University, Brno, Czech Republic.
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$a Eiselleova, Livia $u Faculty of Medicine, Department of Biology, Masaryk University, Brno, Czech Republic.
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$a Stepankova, Veronika $u Faculty of Science, Department of Experimental Biology, Loschmidt Laboratories, Centre for Toxic Compounds in the Environment RECETOX, Masaryk University, Brno, Czech Republic. International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic. Enantis Ltd., Biotechnology Incubator INBIT, Brno, Czech Republic.
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$a Vanova, Tereza $u Faculty of Medicine, Department of Biology, Masaryk University, Brno, Czech Republic.
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$a Brezovsky, Jan $u Faculty of Science, Department of Experimental Biology, Loschmidt Laboratories, Centre for Toxic Compounds in the Environment RECETOX, Masaryk University, Brno, Czech Republic. Faculty of Science, Department of Experimental Biology, Masaryk University, Brno, Czech Republic. International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic.
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$a Damborsky, Jiri $u Faculty of Science, Department of Experimental Biology, Loschmidt Laboratories, Centre for Toxic Compounds in the Environment RECETOX, Masaryk University, Brno, Czech Republic. Faculty of Science, Department of Experimental Biology, Masaryk University, Brno, Czech Republic. International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic.
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