Álex Pérez Sánchez

Lipid mediators, such as prostaglandin E2 (PGE2), play fundamental roles in cellular communication and in the development of diseases like cancer. The lipid mediators interact with specialized proteins called G protein-coupled receptors (GPCRs), with Prostaglandin E2 Receptor Type 4 (EP4) being particularly significant in cancer and inflammation, driving tumor growth, metastasis, and immune evasion. By employing advanced Free Energy Perturbation (FEP) and atomistic Molecular Dynamics (MD) simulations of the receptor-G proteins complex in its native membrane, we study here how PGE2 activates EP4, offering novel molecular insight into the treatment of diseases. In this regard, we unravel the complex interactions between PGE2 and EP4, revealing mechanisms behind receptor and G protein activation process. Our combined findings provide insights into the functional dynamics of for GPCRs for the future development of innovative therapeutic strategies for cancer by targeting key cellular signalling pathways

Lipid mediators, such as prostaglandin E2 (PGE2), play fundamental roles in cellular communication and in the development of diseases like cancer. The lipid mediators interact with specialized proteins called G protein-coupled receptors (GPCRs), with Prostaglandin E2 Receptor Type 4 (EP4) being particularly significant in cancer and inflammation, driving tumor growth, metastasis, and immune evasion. By employing advanced Free Energy Perturbation (FEP) and atomistic Molecular Dynamics (MD) simulations of the receptor-G proteins complex in its native membrane, we study here how PGE2 activates EP4, offering novel molecular insight into the treatment of diseases. In this regard, we unravel the complex interactions between PGE2 and EP4, revealing mechanisms behind receptor and G protein activation process. Our combined findings provide insights into the functional dynamics of for GPCRs for the future development of innovative therapeutic strategies for cancer by targeting key cellular signalling pathways

G protein-coupled receptors (GPCRs) are central players in cellular signaling pathways and represent
prominent targets for drug development in various diseases, including cancer. The EP4 receptor belongs to the
prostaglandin E2 (PGE2) receptor family of GPCRs that has received significant attention due to its
involvement in cancer progression and inflammation. Overexpression of EP4 promotes tumor growth,
metastasis, and evasion of immune surveillance in numerous cancer types. Understanding the molecular
mechanisms underlying the EP4 receptor activation by its endogenous ligand, PGE2, and subsequent
engagement with G proteins is crucial for unraveling its role in cancer pathogenesis and devising targeted
therapeutic strategies. Using atomistic molecular dynamics (MD) simulations in combination with enhanced
sampling methods and free energy calculations, we study here the mechanisms of EP4 receptor activation by
PGE2 and its interaction with G proteins, offering insights into cancer-associated signaling pathways regulated
by this receptor.

Cyclooxygenases are a family of enzymes essential in the regulation of inflammation and other processes in the human body. There are two main isoforms, COX-1 and COX-2, with different roles and patterns of expression in tissues. COX-1 is widely expressed and maintains homeostasis, while COX-2 is restricted to specific regions and it is inducible, especially in at inflamed tissues and cancer cells. COX-2 overexpression is associated with the development of cancer in several types of tumors. To investigate this phenomenon, fluorescent compounds derived from anti-inflammatory drugs are usually experimentally used for the detection of COX-2 in cancer cells.
Using different computational techniques (Molecular Docking, Molecular Dynamics Simulations, QM/MM and TD-DFT Calculations) we have calculated and analyzed the fluorescence spectra of a photochromic compound bound to the monomer and dimer of human COX-2. The differences between the monomeric and dimeric spectra reveals molecular insights of the protein’s behavior in cells with COX-2 overexpressed. This research provides valuable information for the possible future design of specific drugs for cancer treatments.

Exploring Molecular Space. Presented by the Division of Computational and Theoretical Chemistry

Co-supervision of two final bachelor’s degree projects.

Professor for problems sessions of Chemistry Foundations (51.9 hours)

Professor for the computational laboratories of Quantum Chemistry (20 hours)

Chemistry Corrector and Supervisor of Court 329

Professor for the computational laboratories of Quantum Chemistry (20 hours)

Co-supervision of one final bachelor’s degree projects.

Professor for the experimental laboratories of Chemical Bonding and Structure of Matter (12 hours)

Professor for the experimental laboratories of Thermodynamics, Kinetics and Phase Transformations (12 hours)

The advanced course intended to broaden the vision of the potentials of computing in the research and development of new drugs, new materials or new compounds.
The course takes place for a whole week and is mainly addressed to Chemistry, Biology, Pharmacy and Chemical Engineering students.

Photoinitiated processes are important for the understanding of natural phenomena and they also play an essential role in emerging fields as renewable energy, material design and nano-medicine.

Molecular reaction dynamics is the study of elementary processes and the means of probing them, understanding them, and controlling them. It can be applied to reactions in gas phase, in solution and onto surfaces, exploring the elementary steps in catalysis. Nowadays, chemistry requires a molecular level understanding of the reactivity.