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 the laboratory evolution of some retro-aldolase enzymes1,2 is presented. Microsecond time-scale Molecular Dynamics simulations are used to elucidate the changes in the conformational landscape of evolved retro-aldolase variants. Most importantly, our shortest path map analysis tool 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 retro-aldolase enzymes.3 Interestingly, the residues predicted to participate in the conformational sub-state conversions coincide with the mutation points introduced in laboratory evolution for enhancing the novel retro-aldol activity. 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.3,4

Role of conformational dynamics in the evolution of novel retro-aldolase activity

254th National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.