Protein folding and molecular design

 

The ProtMol group is fascinated with protein molecules. We are located in two laboratories affiliated to the Department of Biochemistry and Molecular and Cellular Biology and to the Institute for Biocomputation and Physics of Complex Systems at the University of Zaragoza, respectively. The labs are fully equipped for integrative research using techniques of Cellular and Molecular Biology, Biochemistry, Biophysics, and Computation. For the last 20 years, we have been studying the principles of protein stability, folding and cofactor binding, and trying to understand the relationship between Protein Dynamics and function. During this time we have used a variety of models, such as flavodoxin, to understand protein stability and to develop strategies for protein stabilization. Protein stability is a very important topic from both theoretical and practical perspectives, and we still lack enough quantitative understanding of it. Molecular Biophysics keeps being one of our main fields of activity.

In recent years, we have begun to investigate protein conformational diseases in order to both understand their molecular causes and to discover small molecules that can be developed into new drug therapies. In this endeavor, we combine classical Biochemistry and Biophysics with novel HTP screening techniques, Bioinformatics, Synthetic Chemistry and in vivo testing. Our projects include testing in animal models several antimicrobials effective against the human pathogen Helicobacter pylori, and the rational improvement of novel pharmacological chaperones that can rescue a defective human enzyme (mutated PAH) responsible for Phenylketonuria. At present, we are also testing new compounds that interfere with the aggregation of the b amyloid peptide and of amylin, and we are developing novel chaperones to rescue several defective human enzymes. We are open to proposals from Academia or Industry for collaboration in the discovery of novel bioactive compounds against validated protein targets, specially antimicrobials or pharmacological chaperones.

Rather than in techniques, we are interested in problems and, therefore, we are increasingly combing experimental approaches with computational studies, as needed. We have recently developed a tool (ProtSA) for estimating sequence specific atom accessibilities of proteins in unfolded ensembles. Some of our current computational studies try to address the Molecular Dynamics identification of SNPs involved in conformational diseases, the prediction of local unstable regions of proteins involved in dynamics, and the development of computational aids for protein stabilization.

Our group is pleased to accept talented and motivated doctoral students or postdocs interested in our work. Just contact us if you feel like…