Simulating Substrate Recognition and Oxidation in Laccases: From Description to Design

• Published in: Journal of chemical theory and computation Vol. 13; no. 3; pp. 1462 - 1467
• Main Authors: Lucas, Maria Fátima, Monza, Emanuele, Jørgensen, Lise J, Ernst, Heidi A, Piontek, Klaus, Bjerrum, Morten J, Martinez, Ángel T, Camarero, Susana, Guallar, Víctor
• Format: Journal Article Publication
• Language: English
• Published: United States American Chemical Society 14.03.2017
• Subjects: Analysis; Binding; Computation; Computer simulation; Enginyeria biomèdica; Enzims; Enzyme; Enzyme complexes; Enzymes; Investigació; Kinetics; Laccase; Laccase - chemistry; Laccase - genetics; Laccase - metabolism; Molecular Dynamics Simulation; Oxidation; Oxidation-Reduction; Phenol - chemistry; Phenol - metabolism; Protein Binding; Protein Conformation; Protein Engineering; Proteins; Proteïnes; Substrates; Àrees temàtiques de la UPC
• ISSN: 1549-9618; 1549-9626
• DOI: 10.1021/acs.jctc.6b01158

To meet the very specific requirements demanded by industry, proteins must be appropriately tailored. Engineering laccases, to improve the oxidation of small molecules, with applications in multiple fields, is, however, a difficult task. Most efforts have concentrated on increasing the redox potential of the enzyme, but in recent work, we have pursued an alternate strategy to engineering these biocatalysts. In particular, we have found that redesigning substrate binding at the T1 pocket, guided by in silico methodologies, to be a more consistent option. In this work, we evaluate the robustness of our computational approach to estimate activity, emphasizing the importance of the binding event in laccase reactivity. Strengths and weaknesses of the protocol are discussed along with its potential for scoring large numbers of protein sequences and thus its significance in protein engineering.