Phospholipid nanodiscs are used to stabilize membrane proteins when the protein is removed from its native biological environment by providing interaction with a lipid bilayer, allowing the protein to be isolated without denaturing. An amphipathic polymer ((poly(styrene-co-maleic acid);SMA) has been used to encircle a discoidal lipid bilayer, keeping it from dispersing. Using small-angle neutron scattering (SANS), a structural mapping of the protein may be obtained from this stabilized structure. SMA polymer has a different scattering length density from the membrane protein being stabilized, allowing the protein to be clearly observed using contrast variation.<br/>To confirm experimental results, computer modeling is commonly used to predict the SANS profile of proteins. If the experimentally determined neutron scattering profile matches the theoretical computer generated profile, experimental researchers are reassured their results are valid. Predictive modeling of SANS profiles for membrane proteins was not possible since no suitable nanodisc model had been created, leading to uncertainty in the structure of the membrane proteins being studied. Also, the interaction and orientation between the bilayer and the SMA polymer had not yet been precisely determined through experimental studies. In our research, we used computer modeling and molecular dynamics to construct and simulate a nanodisc. In the process of creating this nanodisc for membrane protein modeling, we simulated the behavior of the SMA polymer belt, providing insight into this interaction. The lipid used was 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) since this lipid was also used in research studies. Parameters for the SMA polymer were developed through CGENFF by analogy to known structures. By analyzing the polymer dihedrals for this initial simulation, we predicted the rotational volume each polymer strand would require, allowing for accurate polymer orientation in the full nanodisc.

Construction and molecular dynamics of a SMA nanodisc for membrane protein simulation

251st National Meeting (2016)

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