Computer simulations to aid rational enzyme engineering

Enzymes in industrial setting

Enzymes are highly selective biological catalysts that enable virtually all chemical reactions in life. Despite their vast potential, industrial applications might be restricted to several catalytic features, since these biocatalysts have evolved to function optimally under biological conditions. For instance, the enzymatic performance under high temperatures or with organic solvents may be decreased, limiting their use in industry. This issue can be tackled through protein engineering, where novel and improved enzymes are designed.

Computer simulations to aid rational enzyme engineering

Experimental protein engineering campaigns provide means to increase enzymatic performance in industrially relevant conditions, although at the cost of performing a large number of wet lab experiments and sometimes lacking a rational perspective. In this regard, computational tools allow us to better comprehend the rationale behind these experimental modifications and further exploit and propose new and better mutations. Consequently, simulations can increase the prediction/success ratio of engineering campaigns, which is ultimately translated into a significant cost reduction.

Research at Nostrum Biodiscovery

Dr. Joan Coines, a senior project manager from the Enzyme Engineering division at Nostrum Biodiscovery, has recently published an article as a part of The Journal of Physical Chemistry virtual special issue“Computational Advances in Protein Engineering and Enzyme Design”. In this publication, the use of computer simulations to aid engineering of glycosidases and glycosyltransferases is discussed, showing two studies where this was applied to both types of enzymes. In particular, a glycosidase was converted into a phosphorylase; and the O/N/S-specificity of a glycosyltransferase was tuned as desired. Both investigations included classical molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculations, combined with enhanced sampling methods such as metadynamics.

Cycle of rational enzyme engineering

Enzyme engineering requires interplay between computational and experimental approaches in order to learn, test and design new and improved variants. Molecular simulations can assist in predicting and further understanding them.

Protein engineering services

At Nostrum Biodiscovery we offer the aforementioned computational techniques to our clients, as well as our in-house proprietary software PELE (Protein Energy Landscape Exploration), an accurate and fast technique to perform substrate exploration while simultaneously predicting the protein structure. With these tools, we are able to fulfill the requirements of our clients and provide efficient, fast and accurate protein engineering services.

Structural-Based Modeling in Protein Engineering. A Must Do

Computer Simulation to Rationalize “Rational” Engineering of Glycoside Hydrolases and Glycosyltransferases