Computational & Systems Biology

Mathematical and Computational Modeling

Redox Biology

Biological Membranes


Systems Biology

Research lines

Connecting design to function in redox signaling and antioxidant protection

Modeling permeation through physiological barriers

Computational tools for biomolecular systems


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.


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Information about journal articles, updated at 26-06-2022, from platform CIÊNCIAVITAE.

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. . 10.3389/fped.2022.875877 . published Frontiers in Pediatrics

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. . 10.3390/membranes12030254 . Membranes

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. . 10.1016/j.redox.2022.102250 . 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. . 10.1016/j.freeradbiomed.2020.07.007 . published Free Radical Biology and Medicine

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. . 10.1021/acs.jctc.8b00150 . published Journal of Chemical Theory and Computation

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. . 10.1016/j.redox.2017.12.008 . published Redox Biology

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. . 10.1016/j.redox.2017.01.003 . published Redox Biology

Mass Isotopomer Analysis of Nucleosides Isolated from RNA and DNA Using GC/MS

Miranda-Santos, Ines; Gramacho, Silvia; Pineiro, Marta; Martinez-Gomez, Karla; Fritz, Michel; Hollemeyer, Klaus; Salvador, Armindo; Heinzle, Elmar, 2015. Analytical Chemistry. 617 - 623. 1. 87. 2015. . 10.1021/ac503305w . published Analytical Chemistry

Beyond Overton's Rule: Quantitative Modeling of Passive Permeation through Tight Cell Monolayers

Filipe, H. A. L.; Salvador, A.; Silvestre, J. M.; Vaz, W. L. C.; Moreno, M. J., 2014. Molecular Pharmaceutics. 3696 - 3706. 10. 11. 2014. . 10.1021/mp500437e . published Molecular Pharmaceutics

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. . 10.1194/jlr.M043067 . published Journal of Lipid Research

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. . 10.1016/j.freeradbiomed.2014.06.007 . published Free Radical Biology and Medicine

Relating mutant genotype to phenotype via quantitative behavior of the NADPH redox cycle in human erythrocytes

Coelho, P.M.B.M.; Salvador, A.; Savageau, M.A., 2010. PLoS ONE. 9. 5. 2010. . 10.1371/journal.pone.0013031 . published PLoS ONE

Quantifying global tolerance of biochemical systems: Design implications for moiety-transfer cycles

Coelho, P.M.B.M.; Salvador, A.; Savageau, M.A., 2009. PLoS Computational Biology. 3. 5. 2009. . 10.1371/journal.pcbi.1000319 . published PLoS Computational Biology

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. . 10.1073/pnas.0809869106 . 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. . 10.1038/nbt0606-667 . published Nature Biotechnology

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. . 10.1073/pnas.0510776103 . published Proceedings of the National Academy of Sciences of the United States of America

Why does superoxide dismutase overexpression often increase hydrogen peroxide concentrations? An alternative explanation

Gardner, R.; Moradas-Ferreira, P.; Salvador, A., 2006. Journal of Theoretical Biology. 798 - 800. 3. 242. 2006. . 10.1016/j.jtbi.2006.04.007 . published Journal of Theoretical Biology

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. . 10.1073/pnas.2335687100 . published Proceedings of the National Academy of Sciences of the United States of America

Why does SOD overexpression sometimes enhance, sometimes decrease, hydrogen peroxide production? A minimalist explanation

Gardner, R.; Salvador, A.; Moradas-Ferreira, P., 2002. Free Radical Biology and Medicine. 1351 - 1357. 12. 32. 2002. . 10.1016/S0891-5849(02)00861-4 . published Free Radical Biology and Medicine

Hydroperoxyl, superoxide and pH gradients in the mitochondrial matrix: A theoretical assessment

Salvador, A.; Sousa, J.; Pinto, R.E., 2001. Free Radical Biology and Medicine. 1208 - 1215. 10. 31. 2001. . 10.1016/S0891-5849(01)00707-9 . published Free Radical Biology and Medicine

Synergism analysis of biochemical systems. II. Tensor formulation and treatment of stoichiometric constraints

Salvador, A., 2000. Mathematical Biosciences. 131 - 158. 2. 163. 2000. . 10.1016/S0025-5564(99)00057-7 . published Mathematical Biosciences

Synergism analysis of biochemical systems. I. Conceptual framework

Salvador, A., 2000. Mathematical Biosciences. 105 - 129. 2. 163. 2000. 10.1016/s0025-5564(99)00056-5 . published Mathematical Biosciences

Lipid peroxidation in mitochondrial inner membranes. I. An integrative kinetic model

Antunes, F.; Salvador, A.; Marinho, H.S.; Alves, R.; Pinto, R.E., 1996. Free Radical Biology and Medicine. 917 - 943. 7. 21. 1996. . 10.1016/S0891-5849(96)00185-2 . published Free Radical Biology and Medicine

PHGPx and phospholipase A2/GPx: Comparative importance on the reduction of hydroperoxides in rat liver mitochondria

Antunes, F.; Salvador, A.; Pinto, R.E., 1995. Free Radical Biology and Medicine. 669 - 677. 5. 19. 1995. . 10.1016/0891-5849(95)00040-5 . published Free Radical Biology and Medicine

Kinetic modelling of in vitro lipid peroxidation experiments--'low level' validation of a model of in vivo lipid peroxidation.

Salvador, A.; Antunes, F.; Pinto, R.E., 1995. Free radical research. 151 - 172. 2. 23. 1995. . 10.3109/10715769509064029 . published Free radical research

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