What do we do?
Our main goal at the Laboratory for Biomolecular Modeling is to understand the physical and chemical properties of complex biological systems, in particular their function with regard to structure and dynamics. To this end, we use and develop a broad spectrum of computational tools fully integrated with experimental data. Multiscale simulations and dynamic integrative modelling are used to investigate the function of molecular assemblies, mimicking conditions of the native cellular environment.
The physical and chemical characterization of biological membranes is of fundamental importance for understanding the functional role of lipid bilayers in shaping cells and organelles, steering vesicle trafficking and promoting membrane-protein signalling. Molecular dynamics simulations stand as a powerful tool to probe the properties of membranes at the atomistic level. However, the biological membrane is highly complex, and closely mimicking its physiological constitution in silico is not a straightforward task.
Using LipidBuilder, a framework that we previously introduced for creating models of biologically relevant phospholipid species with acyl tails of heterogeneous composition, we used multiscale molecular dynamics simulations to investigate the stability of the amyloid precursor protein (APP) dimer in realistic models of the synaptic plasma membrane (SPM). The proteolytic cleavage of the transmembrane domain of APP releases amyloid-β (Aβ) peptides, whose accumulation in the brain tissue is an early indicator of Alzheimer’s disease. We discovered that the specific composition of the SPM and, in particular, the abundance of highly unsaturated lipids were fundamental for selecting one of the two possible APP dimerization states so far proposed (Audagnotto M et al. 2016).
Main publications 2016
- Audagnotto M et al. Effect of the Synaptic Plasma Membrane on the Stability of the Amyloid Precursor Protein Homodimer. J Phys Chem Lett 2016;7:3572.
- Abriata LA et al. Molecular Effects of Concentrated Solutes on Protein Hydration, Dynamics, and Electrostatics. Biophysical Journal 2016;111:743.
- Iacovache I et al. Cryo-EM structure of aerolysin variants reveals a novel protein fold and the pore-formation process. Nature Communications 2016; 7:12062.
- Song AS et al. Immobilization of the N-terminal helix stabilizes prefusion paramyxovirus fusion proteins. PNAS 2016; 113:E3844.