Molecular simulations on membrane-associated proteins have allowed for improved understanding of their mechanism and interpretation of experiments. Our lab researches a wide variety of these proteins from simple channel proteins to active transporters to those that act as signaling proteins. In this talk, a peripheral membrane protein that senses lipid curvature or packing serves as an example of what can be learned by using all-atom molecular dynamics (MD) simulations. The membrane binding of the oxysterol binding protein homologue (Osh4) was studied with ms all-atom MD to probe how this protein might function as an intracellular lipid transport protein. Our results suggest a complex binding motif that is preferred with a single lipid membrane and that lipid exchange between membranes occurs at membrane contact sites that activate this protein. A simple domain of Osh4 is then simulated that is an amphipathic lipid packing sensor (ALPS). All-atom MD and an enhanced sampling technique are used to probe the mechanism of membrane binding and its bound structure. Lipid packing defects are found to enhance membrane binding but too much of a defect can inhibit binding.<br/>

Studies of a peripheral membrane protein in yeast (Osh4) and its peptide that senses lipid packing

2019 Spring National Meeting

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