CNC

Overview

The Computational & Systems Biology Group focuses on two main research lines:

Organization principles of biochemical systems. We seek to discover, understand and exploit generic rules that relate the design of biochemical systems to function, with redox signaling and antioxidant protection in human cells as a main object of study. Hydrogen peroxide regulates multiple fundamental cellular processes (e.g. inflammation, apoptosis, cell proliferation), with strong implications for vascular development and degenerative diseases. However, the principles of this signaling remain mysterious. We apply our know-how in computational modeling and systems analysis and collaborate with leading wet-lab groups to clarify the most fundamental open questions in this area. We seek to achieve clinically actionable insights on how the core thiol-redox system in human cells integrates multiple cellular functions.

Modeling the permeation through physiological barriers. The long-term goal is to develop quantitative structure-activity relationships (QSAR) for the permeation of the blood-brain barrier (BBB). Failure to cross the BBB is the main attrition factor in the development of psycho-active drugs. The bioavailability of xenobiotics at the brain is strongly affected by their interaction with lipid bilayers and blood components. Our work shows that the partition of drugs among the compartments strongly affects the timing and effectiveness of their permeation across the BBB. We are modeling how molecular features of the xenobiotics impact on the kinetics of these critical steps and working to achieve better predictions of overall permeability.

We also develop novel computational approaches to achieve the previous goals.

Featured Articles

Information about journal articles, updated at 17-11-2024, from platform CIÊNCIAVITAE.

Localized redox relays as a privileged mode of cytoplasmic hydrogen peroxide signaling

Travasso, R.D.M.; Sampaio dos Aidos, F.; Bayani, A.; Abranches, P.; Salvador, A., 2017. Redox Biology. 233 - 245. 12. 2017. http://www.scopus.com/inward/record.url?eid=2-s2.0-85014574052&partnerID=MN8TOARS . 10.1016/j.redox.2017.01.003 . published Redox Biology

Hydrogen peroxide metabolism and sensing in human erythrocytes: A validated kinetic model and reappraisal of the role of peroxiredoxin II

Benfeitas, R.; Selvaggio, G.; Antunes, F.; Coelho, P.M.B.M.; Salvador, A., 2014. Free Radical Biology and Medicine. 35 - 49. 74. 2014. http://www.scopus.com/inward/record.url?eid=2-s2.0-84904329372&partnerID=MN8TOARS . 10.1016/j.freeradbiomed.2014.06.007 . published Free Radical Biology and Medicine

Phenotypes and tolerances in the design space of biochemical systems

Savageau, M.A.; Coelho, P.M.B.M.; Fasani, R.A.; Tolla, D.A.; Salvador, A., 2009. Proceedings of the National Academy of Sciences of the United States of America. 6435 - 6440. 16. 106. 2009. http://www.scopus.com/inward/record.url?eid=2-s2.0-66149108427&partnerID=MN8TOARS . 10.1073/pnas.0809869106 . published Proceedings of the National Academy of Sciences of the United States of America

How abundant are superoxide and hydrogen peroxide in the vasculature lumen, how far can they reach?

Tânia Sousa; Marcos Gouveia; Rui D.M. Travasso; Armindo Salvador, 2022. Redox Biology. 2022. https://doi.org/10.1016/j.redox.2022.102527 . 10.1016/j.redox.2022.102527 . published Redox Biology

Mapping the phenotypic repertoire of the cytoplasmic 2-Cys peroxiredoxin – Thioredoxin system. 1. Understanding commonalities and differences among cell types

Selvaggio, Gianluca; Coelho, Pedro M.B.M.; Salvador, Armindo, 2018. Redox Biology. 297 - 315. 15. 2018. http://dx.doi.org/10.1016/j.redox.2017.12.008 . 10.1016/j.redox.2017.12.008 . published Redox Biology

Intra-dimer cooperativity between the active site cysteines during the oxidation of peroxiredoxin 2

Peskin, Alexander V.; Meotti, Flávia C.; de Souza, Luiz F.; Anderson, Robert F.; Winterbourn, Christine C.; Salvador, Armindo, 2020. Free Radical Biology and Medicine. 115 - 125. 158. 2020. http://dx.doi.org/10.1016/j.freeradbiomed.2020.07.007 . 10.1016/j.freeradbiomed.2020.07.007 . published Free Radical Biology and Medicine

In vivo hydrogen peroxide diffusivity in brain tissue supports volume signaling activity

A. Ledo; E. Fernandes; A. Salvador; J. Laranjinha; R.M. Barbosa, 2022. Redox Biology. 50. 2022. https://doi.org/10.1016/j.redox.2022.102250 . 10.1016/j.redox.2022.102250 . published Redox Biology

Glucose-6-Phosphate Dehydrogenase Deficiency and Neonatal Hyperbilirubinemia: Insights on Pathophysiology, Diagnosis, and Gene Variants in Disease Heterogeneity

Lee, Heng Yang; Ithnin, Azlin; Azma, Raja Zahrathul; Othman, Ainoon; Salvador, Armindo; Cheah, Fook Choe, 2022. Frontiers in Pediatrics. 10. 2022. http://dx.doi.org/10.3389/fped.2022.875877 . 10.3389/fped.2022.875877 . published Frontiers in Pediatrics

Quantitative evolutionary design of glucose 6-phosphate dehydrogenase expression in human erythrocytes

Salvador, A.; Savageau, M.A., 2003. Proceedings of the National Academy of Sciences of the United States of America. 14463 - 14468. SUPPL. 2. 100. 2003. http://www.scopus.com/inward/record.url?eid=2-s2.0-0345060788&partnerID=MN8TOARS . 10.1073/pnas.2335687100 . published Proceedings of the National Academy of Sciences of the United States of America

Evolution of enzymes in a series is driven by dissimilar functional demands

Salvador, A.; Savageau, M.A., 2006. Proceedings of the National Academy of Sciences of the United States of America. 2226 - 2231. 7. 103. 2006. http://www.scopus.com/inward/record.url?eid=2-s2.0-33144458377&partnerID=MN8TOARS . 10.1073/pnas.0510776103 . published Proceedings of the National Academy of Sciences of the United States of America

Tools for kinetic modeling of biochemical networks

Alves, R.; Antunes, F.; Salvador, A., 2006. Nature Biotechnology. 667 - 672. 6. 24. 2006. http://www.scopus.com/inward/record.url?eid=2-s2.0-33745075591&partnerID=MN8TOARS . 10.1038/nbt0606-667 . published Nature Biotechnology

Calculation of Permeability Coefficients from Solute Equilibration Dynamics: An Assessment of Various Methods

Margarida M. Cordeiro; Armindo Salvador; Maria João Moreno, 2022. Membranes. 254 - 254. 3. 12. 2022. https://doi.org/10.3390/membranes12030254 . 10.3390/membranes12030254 . Membranes

Quantitative Assessment of Methods Used To Obtain Rate Constants from Molecular Dynamics Simulations—Translocation of Cholesterol across Lipid Bilayers

Filipe, Hugo A. L.; Javanainen, Matti; Salvador, Armindo; Galvão, Adelino M.; Vattulainen, Ilpo; Loura, Luís M. S.; Moreno, Maria João, 2018. Journal of Chemical Theory and Computation. 3840 - 3848. 7. 14. 2018. http://dx.doi.org/10.1021/acs.jctc.8b00150 . 10.1021/acs.jctc.8b00150 . published Journal of Chemical Theory and Computation

Homeostasis of free cholesterol in the blood: A preliminary evaluation and modeling of its passive transport

Estronca, L.M.B.B.; Filipe, H.A.L.; Salvador, A.; Moreno, M.J.; Vaz, W.L.C., 2014. Journal of Lipid Research. 1033 - 1043. 6. 55. 2014. http://www.scopus.com/inward/record.url?eid=2-s2.0-84901660412&partnerID=MN8TOARS . 10.1194/jlr.M043067 . published Journal of Lipid Research

The mammalian peroxisomal membrane is permeable to both GSH and GSSG - Implications for intraperoxisomal redox homeostasis

Ferreira, Maria J.; Rodrigues, Tony A.; Pedrosa, Ana G.; Gales, Luís; Salvador, Armindo; Francisco, Tânia; Azevedo, Jorge E., 2023. Redox Biology. 63. 2023. http://dx.doi.org/10.1016/j.redox.2023.102764 . 10.1016/j.redox.2023.102764 . published Redox Biology

5 15 out of 15 Featured Publications

Publications

Information about journal articles, updated at 17-11-2024, from platform CIÊNCIAVITAE.

Pillars of theoretical biology: "Biochemical systems analysis, I, II and III"

Armindo Salvador, 2024. Journal of Theoretical Biology. 576. 2024. https://doi.org/10.1016/j.jtbi.2023.111655 . 10.1016/j.jtbi.2023.111655 . published Journal of Theoretical Biology

The architecture of redox microdomains: Cascading gradients and peroxiredoxins' redox-oligomeric coupling integrate redox signaling and antioxidant protection

Matthew Griffith; Adérito Araújo; Rui Travasso; Armindo Salvador, 2023. Redox Biology. 69. 2023. https://doi.org/10.1016/j.redox.2023.103000 . 10.1016/j.redox.2023.103000 . published Redox Biology

The mammalian peroxisomal membrane is permeable to both GSH and GSSG - Implications for intraperoxisomal redox homeostasis

Ligand's Partition to the Lipid Bilayer Should Be Accounted for When Estimating Their Affinity to Proteins

Moreno, Maria João; Salvador, Armindo, 2023. Molecules. 7. 28. 2023. http://dx.doi.org/10.3390/molecules28073136 . 10.3390/molecules28073136 . Molecules

Analysis of the Equilibrium Distribution of Ligands in Heterogeneous Media: Approaches and Pitfalls

Maria João Moreno; Luís M. S. Loura; Jorge Martins; Armindo Salvador; Adrian Velazquez-Campoy, 2022. International Journal of Molecular Sciences. 17. 23. 2022. https://doi.org/10.3390/ijms23179757 . 10.3390/ijms23179757 . published International Journal of Molecular Sciences

Modeling Gd<sup>3+</sup> Complexes for Molecular Dynamics Simulations: Toward a Rational Optimization of MRI Contrast Agents

Oliveira, Alexandre C.; Filipe, Hugo A. L.; Ramalho, João P. Prates; Salvador, Armindo; Geraldes, Carlos F. G. C.; Moreno, Maria João; Loura, Luís M. S., 2022. Inorganic Chemistry. 2022. http://dx.doi.org/10.1021/acs.inorgchem.2c01597 . 10.1021/acs.inorgchem.2c01597 . Inorganic Chemistry