Local Fourier Shell Information (FSI) for assessing Biological 3D structures.

• Grant number: 25/02851-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2025
• End date: March 31, 2026
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Marin Gerard van Heel
• Grantee: Joana de Medeiros Oliveira Hulse Molinete
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil
• Associated research grant: 20/06062-1 - Biological complexes in action, in vitro and in silico (Exploiting Big-Data in Cryo-EM), AP.TEM

Abstract

The quality assessment of 3D biological structures, such as that of the SARS-CoV2 spike protein is fundamental for understanding its modus operandi during infection. The assessment of the local quality reveals such issues as: what areas of the trimeric spike protein are flexible or what areas of the spike accessible to antibodies. The glycosylation of the spike proteins, shields the viral particles to make them invisible to the host immune system, and the glycans are the most dynamic parts of the complex and therefore a perfect target for application of our various local quality assessment metrics.Historically, image quality used to be predicted (but not measured) by theoretical metrics like the Abbe or Rayleigh criterion. These criteria are, however, fixed properties of the imaging instrument and are not associated with the sample that is being studied. These metrics always predict the same "instrumental resolution", even if one forgets to switch on the microscope's illumination. The metrics used for assessing 2D imaging and 3D volumetric results ("results resolution"), are the Fourier Ring Correlation (FRC) [Van Heel et al. 1982] and the Fourier Shell Correlation (FSC) [Harauz & van Heel 1986]. However, one fundamental oddity associated with those 45-years old metrics made a re-definition of the concepts necessary. The new metrics: Fourier Ring Information (FRI) and Fourier Shell Information (FSI) eliminate that oddity [Van Heel & Schatz 2020] and these new metrics are particularly effective for assessing in the local information contents of 2D images and 3D volumes in all fields of science and especially for bio-medical applications. These metrics were found to be superior to their 45-years-old predecessors and especially for studying the dynamics of biological complexes. This application aims at assessing the new metrics for studying the dynamics of bio-complexes like glycosylated Spike proteins.