Biological macromolecules energy landscapes with applications in biotechnology and in biomedicine

Abstract

Understanding the relationships between structure, energetics and functional dynamics of proteins is one of the biggest challenges in molecular biophysics. The energy landscape approach has contributed significantly to the understanding of complex molecular systems such as protein folding problem, where minimalist and coarse-grained models have played a key role. Using coarse-grained models and statistical physics approaches, the problems addressed in this project can be divided into three groups:(1) Fundamental issues in the protein folding area. The topics covered are: understanding the diffusion coefficient in the representation of folding, study of the effects of frustration and non-native interactions in the folding process, and the visualization of the folding funnel. These methologies will be applied in the study of conformational transitions associated with protein functions.(2) Statistical approaches in bioinformatics and information processing, which complement the mechanistic computational approaches.(3) The tools developed will be integrated and applied in biotechnology and biomedicine problems. The technological application is on the study of enzymes involved in the generation of bioethanol in a theoretical-experimental collaboration. We use coarse-grained models in the study of the thermal stability of enzymes, focusing on 'in silico' stability optimization of enzymes and proposing site directed mutations to be tested experimentally. An immediate on going application aims at evaluating and optimizing enzyme cocktails used in the second generation bioethanol production. In biomedicine, these techniques have applications in various biological systems. We will investigate questions associated with Zika virus proteins, the estrogen receptor and on prospecting vaccines. (AU)