Methods for protein/enzyme modification, redesign or de novo
design are of the great importance in modern chemical and
pharmacological industry. Recent project will explore possibility of
the haloalkane dehalogenases tunnels re-engineering towards
enzymes with higher selectivity and reactivity towards desired
substrates. The novelty of the proposed project lies in
engineering of catalytic properties of enzymes by modification of
access tunnels. This is a new concept potentially applicable to
other enzymes with buried active sites.
Combination of computational and experimental methods will
provide detailed description of the free energy profiles and
barriers of the passage of water molecules and
substrates/products through Access tunnel. This will provide new
insights into the role of water solvent in the catalytic mechanism
of enzymes and identification of (energy) bottlenecks for the
process of enzymatic catalysis. Understanding of these
mechanisms will broaden our basic knowledge of enzymatic
catalysis, which has important implications in the basic research
as well as in applications. Based on the analysis carried out, it
will be possible to design new haloalkane dehalogenase
mutants with improved catalytic properties. For challenging ligand
access study new computationl methods will be developed to
improve prediction of accurate tunnels re-engineering towards
enzyme desired selectivity and activity. The incomming researcher is Dr. Artur Góra.