Computational and experimental techniques to manipulate protein structure and function hold the potential to make transformative contributions in the most diverse scientific domains. Our laboratory develops and applies protein computational methodologies to design novel functional and therapeutic proteins. Assessment of the computational work is carried by the experimental arm of the laboratory where testing of our computationally generated hypothesis is performed.
Development of Computational Methodologies for protein design
The Fold From Loops (FFL) algorithm was devised to fold and design functional proteins. The major strength of this algorithm, besides speed and accuracy, is the ability to generate conformational ensembles that enable an efficient search for the best amino-acid sequences to yield fully functional proteins. Our laboratory is active in the development of FFL and other algorithms.
Relevant references: Correia B et al. Nature (2014), Procko E et al. Cell (2014)
Protein engineers have extensively used in vitro evolution techniques to alter and refine protein functionality. As any technique in vitro evolution has its own set of limitations, an important aim in at the LPDI is to develop computational algorithms that can guide in vitro evolution experiments improving its feasibility and efficiency.
Relevant references: Azoitei et al Science (2011), Procko E et al Cell (2014)
Up to today, many pathogens still carry a high disease burden and remain elusive to prevention by means of vaccination. New approaches for the development of efficacious vaccines are one of the most pressing needs of our society. In the past, we have had important breakthroughs on the design of novel immunogens that can serve as the foundation of a vaccine for the Respiratory Syncytial Virus (RSV).
Relevant references: Correia BE et al. Nature (2014)
Protein-based drugs (biologics) are one of the fastest growing segments in drug development and approval. In recent years computational design techniques have achieved several successes on the design of protein binders. These novel design methodologies allow to target specific sites critical for function and to repurpose naturally occurring proteins for such applications.
Relevant references: Procko E et al Cell (2014)
Sensing and accurately quantifying small molecules in biological samples remains an unmet challenge in many areas related to health and biotechnology. While very promising sensing platforms have been developed, the limitation remains in the ability of designing high affinity and specific small molecule receptors that can be used in these sensing platforms. To accomplish this project our laboratory will approach this problem using both chemical biology and computational protein design approaches.
Relevant references: Kambe T, et al. JACS (2014); Niphakis MJ et al., Cell (2015) and Griss R et al., Nat Chem Biol.