Speaker: Assistant Prof. Riccardo Capelli
Computational Structural Biology Group, University of Milano, Italy
Title: Data-Driven Simulations and Simulation-Guided Insights: an Integrative Approach.
Abstract: In this seminar I will discuss two cases where we have used an integrative approach combining computational and experimental efforts. In the first case, I will outline the development of a forward model for calculating SAXS and SANS intensities based on the 3D conformations of proteins and nucleic acids. Our method is efficient enough to implement a bias potential on SAS intensities, allowing us to control and refine molecular dynamics (MD) simulations in real time. Using this technique, we conducted an exploration of conformations consistent with experimental data on a large protein complex, gelsolin, and a protein-nucleic acid complex, UP1-microRNA.
In the second case, I will discuss our recent simulations on a human olfactory receptor, 51E2, whose active state was experimentally determined last year. Using plain MD simulations, we elucidated the atomistic-level inactivation mechanism of this G protein-coupled receptor (GPCR), triggered by a calcium ion bound to the protein's transmembrane region containing two acidic residues. Extending our analysis to all human olfactory receptors and GPCRs, we discovered that divalent ions may play a critical role in the inactivation process for nearly all olfactory receptors and about 30% of GPCRs. This hypothesis could guide the next steps in the experimental field, opening a neglected effect in the activity of GPCRs.