Calculation of the heat capacity of an unfolding transition for a folded peptide

Here, students will implement simulations of the peptide at different temperatures, and construct a Heat Capacity (calculation from the fluctuation dissipation theorem) versus Temperature. At the same time, the students can observe the physical unfolding of a peptide in a simulation, which they can otherwise never observe in an experimental setting.

Allostery on Niemann-Pick disease type C1 (NPC1) protein

Simulations of the lysosomal NPC1 protein which is responsible to maintaining cholesterol homeostasis in the lysosomes. The protein transfers insoluble cholesterol from the lysosomal lumen to the lysosomal membrane. The conformations of the lysosomal domains of the protein are surprisingly sensitive to a single bound cholesterol in the membrane cholesterol binding site. The trajectories shown are from three sample simulations. POPC: simulations without any cholesterol. POPC-CHOL-bound: Simulation with a single cholesterol bound to the protein in the membrane. POPC-CHOL: Simulation with 20% cholesterol in the membrane. Remarkably, 20% cholesterol has little impact on the conformations of the luminal domains.

Original Paper:

(accepted in PLoS Computational Biology)

Spontaneous ion-binding to the Na, K pump

The spontaneous binding of 2 K+ ions to the E2P (outside open) state of the Na, K pump.

Original Paper:

Reorientation of oxidised tails in lipid membranes

Reorientation of oxidised lipids tails in a POPC-PazePC mixture. PazePC is a lipid which has one shortened acyl chain capped by a carboxylate group. The carboxylate group reorients towards the membrane surface, significantly changing the chemistry near the membrane surface.

Original paper:

The formation of triglyceride blisters: early states in lipid droplet formation

Neutral lipids such as triglycerides (TGLs) aggregate inside lipid membranes. Such aggregation is the first step towards lipid droplet biogenesis. The coarse-grained simulations demonstrates spontaneous self-assembly of TGLs in a POPC membrane.

Original paper:

The binding of drugs membranes

Phenothiazines are anti-pyschotic drugs which can be repurposed for use against antibiotic resistance mycobacterium tuberculosis. The simulations shows the binding of the drug on a POPC:POPS membrane.

Original Paper:

Induction of membrane curvature by annexin proteins

The annexins are a family of Calcium-dependant membrane binding proteins, and are responsible for membrane repair. The Annexin machinery is overexpressed in cancer cells which are susceptible to membrane lesions. The membrane repair function of annexins is closely linked to their ability to aggregate as trimers and induce local membrane curvature. The animation shows the binding of human Annexin A4 to a membrane containing 20% POPS lipids.

Original Paper: