Brannigan Lab

Insulin, with amino acids colored by their predicted sensitivity to mutation.  Mutations to red residues are likely to be pathogenic, while mutations to blue residues are likely to be benign. Grey residues had no prediction available. Mixed coloring indicates a mix of predicted effects. Predictions made using EVE (https://evemodel.org/).

Lipids are extremely flexible small molecules. This is made more obvious as the lipid is phased out of a system during a free energy perturbation simulation. In these simulations, they system starts in a "normal" state - all the atoms are interacting with all the other atoms. But as the simulation progresses, the interactions between the lipid of interest (here POPG) and the rest of the simulation are turned off. The relative rigidity of the protein (ELIC) is emphasized by being represented as a crystal-like surface (blue). This is contrasted with the molten, liquid-like appearance of the POPG molecule (brass). The transparency of the lipid approximately corresponds to the strength of its interactions with the rest of the simulation system. Water and other lipids not shown.

Similar to lasagna, cell membranes are layered structures. Just as the pasta layers in lasagna provide essential support for the meat, cheese, and sauce, the cell membrane offers structural support crucial for the cell's survival. Without a membrane, a cell would resemble a lasagna without pasta, a mess.

Unlike folded proteins that have specific native states, IDPs are unstable and fluctuate in space, twisting and turning, stretching and shrinking. BDNF (orange) is shown to exist in an ensemble of conformations, vibrating at different speeds over a short period of time. It moves in a staccato manner similar to a small orange fish swimming through the waters of a fast-paced river.

Left: This image is from a coarse-grained simulation of the open structure of BamA, the beta-barrel and surrounding lipids are in blue. Water within 8 angstroms of the protein is shown in red. This coarse-grained structure can be backmapped to atomistic resolution. Right: This image is from an atomistic simulation of the closed structure of BamA, the beta-barrel and surrounding lipids are in brown. There is a lipid trapped in the center of the beta-barrel shown in white. Water within 10 angstroms of the protein is shown in blue. This atomistic structure is used as the starting point for coarse-graining.

5j8v the breaker of programs, blobulated by the VMD blobulator GUI. Without the GUI, using just the blobulate proc feature, this would take 20 to 30 minutes of entering graphical representation settings in VMD.

The transmembrane domain of the nicotinic acetylcholine receptor, as it would have been decorated if it were a Burger King in the 90s.

Amyloid beta (purple), alpha-synuclein (red), and huntingtin (blue) are well-known IDPs involved in the development of Alzheimer’s, Parkinson’s, and Huntington’s disease respectively and are shown in their awareness colors. Uncovering the “fuzziness” of an IDP may spread light on its function, possibly paving the road to therapeutics for these neurodegenerative diseases.

In each image the accessible conformations are represented as a cloud around a representative pose from the respective phase. The three phases are (left to right) bulk POPC membrane, gas, and annihilated. The annihilated phase is like gas phase but all non-bonded interactions have been turned off allowing the lipid to pass through itself.

A POPC Membrane with two 2 nm gold nanoparticles embedded in it. We observe two polar nanoparticle covered in hydrophobic ligands aggregating. Nanoparticles cause unfavorable membrane conformations due to the exposed regions interacting with water. The membrane rearranges aggregating nanoparticles with ligands splayed open, alleviating unfavorable lipid configurations.

Wildtype ELIC colored by contiguous hydrophobicity (blobs), defined by the blobulator. Blob type assignment is a result of blobulation settings chosen to detect transmembrane domains. p- (polar) and s- (short) blobs are colored orange and green, respectively, h-blobs (hydrophobic) are slightly opaque and colored blue.

The video shows two perspectives on decoupling. The left panel shows the view of the protein/environment while the right panel shows the view of the lipid. The audio is the raw value of the delta E (the difference in energy between adjacent lambda windows); higher volume corresponds to larger values of delta E. The first half of the video is quite tame because only electrostatics are being decoupled - the environment and the lipid still “see” each other for the most part. The Van der Waals interactions are then scaled out over the second half of the video denoted by both a change in volume and the visual fading of either the lipid (left) or environment (right). The last moments of the audio have a rapid increase in volume as we approach the discontinuity between slightly coupled and fully decoupled.

The image shows 5 nanometer gold nanoparticles embedded in a POPC membrane. The POPC headgroups are shown in a iceblue, tails are in purple, GNP’s are shown in cyan, and ligands are hidden. These GNP’s bend the membrane into various shapes leading to areas of high curvature.

The pleats of the skirt represent the trajectory-averaged height of the outer membrane C1A/B beads as a function of r and theta. Coloring indicates mean curvature of the membrane surface. Positive curvature is shown in blue; and negative curvature is shown in red.

The lilac beads represent the phosphate head groups. The multicolor chains represent POPC and the purple-ish secondary structure protein is Gramicidin A (warning: Gramicidin A is not a protein, it is a peptide). The bubbles represent water beads.

SDS micelles coming into contact just before fusing together! The negatively charged headgroups are shown in red, and hydrophobic tails are shown in yellow.

The F0F1 ATP Synthase is a highly conserved mitochondrial membrane protein, responsible for ATP synthesis. It synthesizes ATP using a proton gradient across the membrane. Ice worms have a unique Histidine-rich extension in the APT6 subunit (shown in cyan) that is hypothesized to accelerate proton flow across the membrane, thus producing more ATP levels than the energetic demand of ice worms. Shown in pink and cyan is the predicted structure of the ice worm F0 domain embedded in a POPC bilayer.

The Erwinia ligand-gated ion channel (ELIC) is a bacterial homolog and model system for important neuronal membrane proteins. Ligand-gated ion channels typically only open after binding a ligand. Membrane lipids, however, can have a tremendous impact of the function of these membrane proteins. POPG is shown in pink; transmembrane helix 1 (M1) in blue; M2 in orange; M3 in green; M4 in yellow. Portions of the protein not immediately relevant to the binding pocket are shown in gray.