Heterogeneous nucleation of protein crystals from the application of metal-organic frameworks

• Grant number: 23/17742-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2024
• End date: December 31, 2024
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Ana Carolina de Mattos Zeri
• Grantee: Gustavo Duarte Verçosa
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil

Abstract

The relationship between the three-dimensional structure of proteins and their functions is well-established, in which the arrangement of atoms determines the folding and, consequently, the shape and activity of the protein. Therefore, when analyzing the structure of these macromolecules, it is possible to identify mechanisms related to biological action and develop drugs that modulate these functions. X-ray diffraction crystallography is the most commonly used method to obtain information about the three-dimensional structure of macromolecules. However, an experimental challenge is obtaining protein crystals that are sufficiently well-ordered to allow high-quality diffraction. This is because the crystallization of biological macromolecules is an empirical process, based on trial and error, which requires large quantities of pure and monodisperse protein, as well as high costs for reagents. An alternative to improve the efficiency of this process has been the implementation of heterogeneous nucleation using nanomaterials with high surface area, the ability to form porous networks, and surface functionalization. These materials enhance crystallization by optimizing conditions, allowing the growth of crystals under metastable conditions, and increasing the reproducibility of experiments. In this Scientific Initiation project, an investigation will be conducted centered on one of the zeolitic imidazolate frameworks (ZIFs), ZIF-8. The main objective is to synthesize these metal-organic structures (MOFs) to explore the directed nucleation of protein crystals and analyze the underlying molecular interactions in this process. In addition, studies related to the molecular weights of macromolecules and the application method will be addressed to deepen the understanding of the mechanisms governing crystal formation.