Studies of energy landscapes of biological macromolecules

Abstract

The approach of energy landscapes has significantly contributed to the understanding of complex molecular systems such as the protein folding problem. In this scenario, minimalist and simplified models have played a key role. This project will focus on biological macromolecules, in which we will study the energy landscape of proteins and RNAs using simplified computational models and statistical physics approaches. The central idea is related to the visualization of the energy landscapes, exploring a technique developed by our group at IBILCE-UNESP. This method called the Energy Landscape Visualization Method (ELViM). It is designed for visualization of the protein folding funnel and has excellent potential for detailing molecular mechanisms by going beyond one-dimensional representation. We will extend this methodology to apply to more complex and challenging systems. Topics to be addressed are: (i) visualization of energy landscapes of proteins without a defined native structure, which are intrinsically disordered proteins (IDPs); (ii) RNAs, which have multiple reference structures; and (iii) visualization of energy landscapes of proteins involving hierarchical folding or topological nodes. In parallel with these specific objectives, the methodologies developed and used by our group will be applied to problems involving collaborations outside IBILCE-UNESP, such as estrogen receptor, drug studies with applications in malaria treatment and forensic problems. (AU)