Projects

In this project in the field of theoretical molecular biology we aim to apply the most powerful tools of theoretical chemistry (quantum chemistry, statistical mechanics and biomolecular simulations) to the central problems of the biotechnological and pharmaceutical industry. Our two overarching goals are the design (and in some cases the design of their biocatalytic production) of two different types of drugs that may play a particularly important role in the control and treatment of several potentially serious human diseases: lipoxygenase-related drugs and cyclooxygenases. . for inflammatory diseases and photoswitch drugs. We split the project into two large work packages (wp) a and b: wp a. Drugs related to lipoxygenases and cyclooxygenases for inflammatory diseases. A thorough understanding of the biosynthetic pathways for specialized pro-resolution lipid mediators is imperative in order to develop the most effective chronic inflammation therapies. This will enable the activation of endogenous resolution pathways as well as new therapeutic approaches such as obtaining efficient exogenous drugs for the treatment of human diseases involving severe chronic inflammation, including covid-19. Wp a.1. Biosynthetic pathways of lipoxins and resolvins. Design of NSAIDs that induce the behavior of COX-2 lipoxygenase, thus contributing to the formation of specialized pro-resolution lipid mediators and the resolution of inflammation. Wp a.2. Maresinas (macrophage mediator in the resolution of inflammation). We intend to use computational protein engineering to design an artificial enzyme that can synthesize maresin 1. Wp a.3. Maresina receivers. We will study the mechanism of interaction between maresin 1 and its receptors and try to design other agonists with a more efficient pro-resolution effect. Wp a.4. Allosteric inhibition of mammalian 15-LOX-1. Design of a molecule that maximizes inhibition of 15-LOX-1-catalyzed oxygenation (dimer) of linoleic acid but minimizes the effect on arachidonic acid oxygenation. Wp a.5. “coxib” photoswitches. Design of simple photoswitches by incorporating an azobenzene photoswitch into the original molecule, which allow their reversible local photocontrol in real time. Wp b. Photoswitch drugs. Wp b.1. Development of monophotonic photoswitches in the bio-optical window. Wp b.2: desenvolupament de fotointerruptors multifotònics per a ús en fotofarmacologia. We will focus on three types of azobenzene photoswitches: 1) mag derivatives, which act on synaptic receptors. 2) photoswitch muscarinic agonists, which can optically monitor cardiac function. 3) related to methotrexate, a chemotherapy drug widely prescribed to treat cancer. In parallel with this project, after the experimental validation of our computational designs, several valorization actions will be launched in collaboration with the valorization and patents office of the uabs: presentation of the corresponding patent applications , market analysis of our designs in the biotechnology sector and pharmaceutical companies. , and possible negotiation of a license agreement with interested pharmaceutical and biotech companies.