Andrea Pasquadibisceglie, PhD - "Modelling the Dynamics of Membrane Transporters

Andrea Pasquadibisceglie, PhD
Science for Life Laboratory
Department of Applied Physics
KTH Royal Institute of Technology
Solna, Sweden


Short CV

Abstract
Membrane transporters are responsible for the homeostasis of numerous solutes across all different compartments of our cells. Given their role, mutations and dysregulation of these proteins are often involved in several human pathologies. The large conformational change needed for the translocation is usually triggered by solute binding into the transporter cavity. However, other mechanisms (e.g., proton coupling) or the lipid environment can be critical for the protein functioning. The complexity of these molecular processes represents a hard challenge for biochemical and structural studies. Recent improvements in algorithms and hardware made it possible to use artificial intelligence for extensive biomolecular modelling studies. However, knowing just one or a few conformational steps of the transport cycle is often insufficient to understand the complete mechanism. To this end, we combined AI-driven modelling techniques and physics-based methods to model and simulate the conformational ensemble of different membrane transporter families. With a better understanding of the molecular mechanism, we can identify residues critical for the correct functioning of these proteins, guiding the experimental design of new modulators or the protein itself