A new concept for molecular engineering of artificial enzymes: a multiscale simulation.

We propose a new concept for the design of artificial enzymes from synthetic protein-like copolymers and non-natural functional monomers which in terms of their affinity for water can be divided into two categories: hydrophobic and hydrophilic. Hydrophilic monomers comprise catalytically active groups similar to those in the corresponding amino acid residues. A key ingredient of our approach is that the target globular conformation of protein-like, core-shell morphology with multiple catalytic groups appears spontaneously in the course of controlled radical polymerization in a selective solvent. As a proof of concept, we construct a fully synthetic analog of serine hydrolase, e.g.α-chymotrypsin, using the conformation-dependent sequence design approach and multiscale simulation that combines the methods of "mesoscale chemistry" and atomistic molecular dynamics (MD). A 100 ns GPU-accelerated MD simulation of the designed polymer-supported catalyst in the aqueous environment provides valuable information on the structural organization of this system that has been synthesized in our Lab.