Protein design applying computational biology with Rosetta

• Grant number: 17/17544-4
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): November 01, 2017
• Effective date (End): October 31, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Fabio Cesar Gozzo
• Grantee: Allan Jhonathan Ramos Ferrari
• Supervisor: David Baker
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Research place: University of Washington, United States
• Associated to the scholarship: 16/13195-2 - Modeling of protein structure and protein complexes using mass spectrometry data, BP.DR

Abstract

Natural occurring proteins mediates several biological functions, from the use of solar energy to manufacture complex molecules and sensitive detection of small molecules (olfactory receptors) and light (rhodopsin) to conversion of pH gradients into chemical bonds (ATP synthase). Interestingly, only a small fraction of protein sequence space has been sampled by nature. Evolution proceeds by incremental mutation and selection and, therefore, proteins are clustered tightly into families and not uniformly distributed over full sequence space. De novo protein design aims to explore new functionalities from sequences not found in nature. This approach is founded in the hypothesis that a folded protein corresponds to the lowest energy state of its amino-acid sequence. Two challenges in implementing this approach arise: first, the energy of a system cannot be computed with perfect accuracy; and second, the space of possible structures and sequences is very large and therefore difficult to be thoroughly searched. Professor Baker is the current leader in computational biology applied to protein structure prediction and design. In this project, the physical and statistical basis for energy function calculation used in Rosetta for protein structure prediction and design as well as their sampling strategies are briefly discussed. Some important milestones in the field are highlighted pointing that protein design is a robust computational methodology with huge biotechnological application. At the end of this research internship abroad, it is expected that a full protein design protocol has been developed, from computational and molecular biology strategies to structural characterization of new proteins.