Oral Presentation 2014 International Biophysics Congress

Lipase enzyme interactions with lipid membranes (#180)

Nathalie Willems 1 , Mark Sansom 1
  1. University of Oxford, Oxford, UK

The immobilisation of enzymes has played an instrumental role in the development of the biotechnological industry. The advantages offered by immobilisation, such as increased enzyme stability and up-scaling of processes, have spurred intense experimental investigation into optimising enzyme-surface interactions. The lipase class of enzymes has been the subject of much research due to its relevance in a range of applications. However, specific factors such as how immobilisation affects the structural dynamics, stability, and activity of enzymes remain unclear. In order to develop a more detailed understanding of how different surfaces affect the conformational dynamics of the enzyme in question, one needs access to high-resolution structural data. Here, we apply a multi-scale molecular dynamics (MD) approach to investigate these types of questions.

Using coarse-grained molecular dynamics (CG-MD), we can simulate interactions within model systems involving different lipase enzymes and membrane surfaces. From these systems, we are able to assess the residues implicated in enzyme-bilayer interactions, and derive conclusions about possible binding modes involved depending on the lipid composition of the membrane. Both CalA and M37 enzymes display a common interfacial activation mechanism observed in many lipase enzymes, and we can assess how interactions with a fluid membrane influence the dynamics of the regions implicated in this activation process. The CG simulations can then be refined to atomistic representations to provide more detail regarding the forces and residues that drive these interactions. This information can be used to provide predictive insights that focus on optimising enzyme stability and binding, in the context of enzyme immobilisation.