Changes in a phospholipid bilayer induced by the hydrolysis of a phospholipase A(2) enzyme: A molecular dynamics simulation study

Phospholipase A(2) (PLA(2)) enzymes are important in numerous physiological processes. Their function at lipid-water interfaces is also used as a biop hysical model for protein-membrane interactions. These enzymes catalyze the hydrolysis of the sn-2 bonds of Various phospholipids and the hydrolysis p roducts are known to increase the activity of the enzymes. Here, we have ap plied molecular dynamics (MD) simulations to study the membrane properties in three compositionally different systems that relate to PLA(2) enzyme act ion. One-nanosecond simulations were performed for a 1-palmitoyl-2-linoleoy l-sn-glycero-3-phosphatidylcholine (PLPC) bilayer and for two of its PLA(2) -hydrolyzed versions, i.e., bilayers consisting of lysophospholipids and of either free charged linoleate or free uncharged linoleic acid molecules. T he results revealed loosening of the structure in the hydrolyzed bilayer du e to increased mobility of the molecules in the direction normal to the bil ayer. This loss of integrity due to the hydrolysis products is in accord wi th observations that not only the presence of hydrolysis products, but also a variety of other perturbations of the membrane may activate PLA(2). Addi tionally, changes were observed in other structural parameters and in the e lectrostatic potential across the membrane-water interface. These changes a re discussed in relation to the simulation methodology and the experimental observations of PLA(2)-hydrolyzed membranes.