Membrane-active protein interactions with phospholipid bilayers

Speaker: Mohammad Hassan Khatami (UOIT)

Membrane-active proteins are a class of proteins that interact with lipid membranes in the body. We study two kinds of membrane-active proteins, antimicrobial peptides (AMPs) and lung surfactant (LS) proteins. In the first part I will present results of MD simulation studies of two AMPs from Cod, Gaduscidin-1 and -2 (GAD-1 and GAD-2). These peptides are histidine rich and thus expected to exhibit pH-dependent activity. In this work, we have performed molecular dynamics (MD) simulations with the peptides in both histidine-charged and histidine-neutral forms, along with POPC lipid molecules, employing GROMACS software and an OPLS-AA force field.
In the second part, I will present computational simulations on lung surfactant protein B (SP-B) interacting with lipid bilayer. SP-B is a hydrophobic protein with 79 residues, from the saposin superfamily. Because of the extreme hydrophobicity of SP-B, the experimental structure of the protein is unknown. Thus, we combined the Mini-B (a fragment of SP-B) experimental structure and homology modeling based on proteins in saposin family to construct our initial model of SP-B. Similar to the first part, we employ GROMACS software and an OPLS-AA force field to run our simulations. Our results demonstrate energetically feasible structures for SP-B and provide hypotheses for how SP-B promotes the rearrangement of planar lipid bilayers.
Besides, we were able to predict 15N solid-state NMR spectra of my computational SP-B structures. These predicted spectra indicate that uniform 15N-labelling is unlikely to constrain SP-B’s structure and topology very much and it will likely be necessary to use a more specifically labeled sample for these experiments.