Improving protein binding, in silico approach

Jiří Černý

Institute of Biotechnology AS CR, v.v.i., Vídeňská 1083, CZ-142 20
Prague, Czech Republic

Keywords: protein engineering, protein ligands, cytokines

The ligand engineering group at the Institute of Biotechnology develops peptide/protein ligands for high affinity and high specificity binding of different cytokine molecules. Powerful experimental tools of molecular biology such as ribosome display are successfully combined with theoretical and computational tools including bioinformatics, homology modeling, and molecular dynamics. For example, analysis of available crystal structures, computational energy calculations, and preliminary screening are necessary for suggesting residues that should be randomized in the first round of screening by the ribosome display. This step of computer-aided analysis is then followed by the rational improvement of high affinity mutants from ribosome display. Theoretical protocols for choosing the most probable residue candidates for in vitro mutagenesis will be presented. We will also compare roles of different theoretical methods and their interlocking with the experimental procedures that led to ligand improvements in our laboratory.

Acknowledgements. The support of the Institute of Biotechnology AS CR, v.v.i. (AV0Z50520701) is acknowledged.