Lecture: 'Role of conformational dynamics in the evolution of enzyme function'
Dra. Sílvia Osuna (ICREA Research Professor - Institut de Química Computacional i Catàlisi - UdG)
CiQUS Seminar Room
12:30h
Enzymes exist as an ensemble of conformations important for their function. By introducing mutations to the enzyme sequence, the populations of the different conformational states can be gradually tuned for allowing novel function. In this talk, the population shift induced by distal and active site mutations introduced along a series of laboratory-evolved enzymes is presented. Microsecond time-scale Molecular Dynamics (MD) simulations in combination with correlation-based analysis and Markov State Models (MSM), are applied to elucidate the changes in the conformational landscape of evolved variants. Dramatic changes in the conformational dynamics of active site loops involved in substrate entrance and product release are revealed, which provide a rationalization for the enhancement in catalytic activity of the new evolved variants. Most importantly, our new tools based on inter-residue correlations observed along the microsecond-scale MD simulations provides a strategy to identify the amino acid positions that influence the dynamic properties of laboratory-evolved enzymes. Our method is therefore able to rationalize, but most importantly to predict which residues situated far away from the active site can have a large impact on the enzyme catalytic activity.
About
Sílvia Osuna received her PhD in 2010 from the University of Girona (UdG) at the Institut de Química Computacional (IQC) under the supervision of Prof. Miquel Solà and Prof. Marcel Swart. In 2010, she moved to the group of Prof. Houk at the University of California, Los Angeles (UCLA) thanks to the IOF Marie Curie fellowship. Since then, Sílvia has worked in computational design of enzymes of medical and pharmaceutical interest. She currently holds an ICREA research position at the Institute of Computational Chemistry and Catalysis (IQCC) at the University of Girona. Sílvia has more than 60 research publications, and been recently awarded the Young Researcher award by the Royal Spanish Society of Chemistry (RSEQ 20116), the Research award by the Fundación Princesa de Girona (FPdGi 2016- Science category), and the 2017 Young Investigator Award of EuCheMS Organic Division. Her group works in the computational design of enzymes of medical and pharmaceutical interest, and is funded by the European Research Council project Starting Grant (ERC-2015-STG-679001, NetMoDEzyme).