We seek a quantitative understanding of proteins thermodynamics that allows us to govern the composition of protein ensembles. Using a variety of biophysical techniques, we determine the essential thermodynamic magnitudes of the protein folding equilibrium (ΔG, ΔH, ΔS and ΔCp) in wild type proteins and in variants obtained using protein engineering techniques.
We analyse Molecular Dynamics simulations to increase our understanding of the basic principles. We try to understand the contribution of fundamental interactions (e.g. different types of electrostatic interactions) but also of chemical entities (side chains of amino acid residues) to protein stability. We aspire to provide conceptual and computational tools to make posible a truly quantitative design of protein stability.
We use our knowledge to develop drugs that target proteins, either human or otherwise. We can start from a defined protein target, identify hits, and develop them into leads using a full medicinal chemistry approach.
Our more advanced projects relate to novel bug-specific antimicrobials against Helicobacter pylori, personalized pharmacological chaperons for phenylketonuria, and novel aggregation inhibitors for Parkinson disease.
We are developing techniques to increase the accuracy of phenotipic interpretation of single nucleotide genetic variants. We try to boost the use of MD techniques to accurately classify genetic variants into benign and deletereus. We focus in missense variants affecting regions coding for proteins with a well defined function.
Among others, we work in the interpretation of variants in genes related to diseases screened in the newborn