Abstract
Proteins exert their function by binding to other partners, interacting with other proteins and/or ligands. Protein-protein interactions (PPIs) occur on specific protein surface areas, where few residues (hot spots) largely contribute to binding free energy; their mutations may affect pathways, causing diseases. Autism spectrum disorder (ASD), a major neurodevelopmental disorder, presents molecular mechanisms still unclear. To investigate them, we are designing a protocol to assess the biophysical impact of genetic mutations in PPI networks where autism risk converges. Though no single biological process leads to ASD, studying synaptic mechanisms microscopically may improve our understanding. Our protocol integrates bioinformatic/genetic data (30,000 complexes) from UK/USA collaborators with our molecular studies. Hot spots will be characterized via machine learning (Germany). Results will support: 1) molecular dynamics simulations, 2) variant effects in PPI hubs, 3) in vitro studies.
Project details
Unibo Team Leader: Francesco Musiani
Unibo involved Department/s:
Dipartimento di Farmacia e Biotecnologie
Coordinator:
Università degli Studi di CAGLIARI(Italy)
Total Unibo Contribution: Euro (EUR) 46.047,00
Project Duration in months: 24
Start Date:
28/09/2023
End Date:
28/02/2026
