Molecular Modeling of Macromolecular Systems of Biotechnological Interest

• Grant number: 24/20300-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2025
• End date: October 19, 2025
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Physical-Chemistry
• Principal Investigator: Munir Salomao Skaf
• Grantee: Wagner Augusto Müller
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 13/08293-7 - CCES - Center for Computational Engineering and Sciences, AP.CEPID

Abstract

In this project we propose to carry out computational studies on the nanomorphology of Extracellular Matrices (ECM), such as plant cell walls and bacterial biofilms, aiming to provide insights into the molecular mechanisms underlying their degradation catalyzed by carbohydrate-active enzymes. The project constitutes natural extensions of current research that our group has been developing within the Cepid CCES. Firstly, it is expected that the key enzyme families active on polysaccharides derived from lignocellulosic biomass (which have been extensively studied at CCES) will also show significant activity against the exopolysaccharides (EPS) in biofilms, particularly those decorated glycans found in E. coli and other biofilm extracellular matrices, which are known to be difficult to remove from solid surfaces. However, the enzymatic mechanisms behind biofilm degradation remain largely unknown, making this an essential focus of our proposed research at CCES. Secondly, the molecular nanoarchitecture of ECM, with microbial biofilms being a prominent example found in many biotechnological settings, remains underexplored.¿ Moreover, nanofibrillated cellulose, an important class of extracellular polymeric matrices in biotechnology, has poorly understood molecular mechanisms of production, especially in different solvent environments. Here, we propose using molecular modeling techniques, including classical and hybrid quantum-classical molecular dynamics simulations (MD and QM/MM), as well as first-principles molecular theories of solvation, to elucidate physical-chemical properties of these ECM substrates at the molecular level and to explore means of improving their degradation via enzymatic attack. Detailed analysis of enzyme interactions with biofilm matrix substrates can lead to relevant advances, which benefit public health as well as the medical, food, and industrial sectors.