Research Lab

Computational Biochemistry

Computational Biochemistry
Research Interests

Computational enzymatic catalysis, protein dynamics, computational mutagenesis, molecular docking and drug discovery, all aiming at a better understanding of the functions and applications of enzymes.

Research Highlights
Improving the Catalytic Power of the DszD Enzyme for the Biodesulfurization of Crude Oil and Derivatives

The human civilization has been using enzymes to its benefit for centuries. Due to the vast applications enzymes can have, they are also very attractive for application in industrial processes. However, the natural catalytic rate that, most of the time, enzymes have, are not satisfactory for industry. For that reason, the engineering of enzymes with the purpose of enhancing their catalytic rate has been a popular field in the past years. The application of computational methods to predict mutations that can enhance the catalytic power of enzymes can have a great contribution to the field. This is because it allows a more rational and directed way to mutate the enzymes, which can save a huge amount of time and resources when compared to the practice of produce mutations at random that is generally used.


In the work presented, we used computational methods to predict mutations that enhance the catalytic rate of DszD, an enzyme that intervenes in the 4S pathway together with DszA, DszB and DszC. The 4S pathway has the potential to be used as a biodesulfurization process of crude oil and be an alternative to the currently used processes, which are very costly not only energetically but also for the environment.


Improving the Catalytic Power of the DszD Enzyme for the Biodesulfurization of Crude Oil and Derivatives

Understanding the Catalytic Machinery and the Reaction Pathway of the Malonyl-Acetyl Transferase domain of human Fatty Acid Synthase

Human fatty acid synthase (hFAS) is a large multienzyme that catalyzes all steps of fatty acid synthesis, which is overexpressed in many cancer cells. Studies have shown that FAS inhibitors exhibit antitumor activity without relevant effects over normal cells. Therefore, the molecular description of active sites in hFAS should stimulate the development of inhibitors as anticancer drug candidates. The malonyl-acetyl transferase (MAT) domain is responsible for loading acetylCoA and malonyl-CoA substrates to the acyl-carrier protein (ACP) domain, a carrier for fatty acid reaction intermediates. In this work, we have applied computational QM/MM methods at the DLPNO–CCSD(T)/CBS:AMBER level of theory to study the MAT reaction mechanism.

The results from this work encourage future studies that aim for the full comprehension of the MAT catalytic reaction and for the rational design of novel antineoplastic drugs that target this domain.



Representative Projects

  • “DESignBIOtecHealth: new technologies for three health challenges of modern societies: diabetes, drug abuse and kidney diseases”, FEDER-Norte2020, Total funding: €3.4M, Unit funding: €239,155, Maria João Ramos (PI)
  • “TCCM - Theoretical Chemistry and Computational Modelling”, EC-H2020, Total funding: €3.8M ,Unit funding: €362,000, Maria João Ramos (local PI)
  • “New Biocatalysts for Green Crude Oil Desulfurization”, FCT-MCTES, Total and Unit funding € 239,819, Pedro Alexandrino Fernandes (PI)
  • Gas@BIOMAT - Dipeptide Crystals as Biomaterials for Gas Purification”, FCT-MCTES, Total and Unit funding: €237,566, Alexandre Magalhães (PI)

Selected Publications

Ramos, MJ; Fernandes, PA. 2018. Structure, Dynamics, and Energetics of ATP Hydrolysis by ABC Transporters. ACS Central Science, 4, DOI: 10.1021/acscentsci.8b00631
Sousa, Sérgio F; Neves, Rui PP; Waheed, Sodiq O; Fernandes, Pedro A; Ramos, Maria J. 2018. Structural and mechanistic aspects of S-S bonds in the thioredoxin-like family of proteins. BIOLOGICAL CHEMISTRY, 0(0), DOI: 10.1515/hsz-2018-0319
Cerqueira, NMFSA; Fernandes, PA; Ramos, MJ. 2018. Visualizing the Microscopic World. Interdisciplinary Sciences-Computational Life Sciences, 10, DOI: 10.1007/s12539-017-0255-2
Pereira, AT; Ribeiro, AJM; Fernandes, PA; Ramos, MJ. 2017. Benchmarking of density functionals for the kinetics and thermodynamics of the hydrolysis of glycosidic bonds catalyzed by glycosidases. INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, 117, DOI: 10.1002/qua.25409
Moreira, C; Ramos, MJ; Fernandes, PA. 2017. Clarifying the Catalytic Mechanism of Human Glutamine Synthetase: A QM/MM Study. JOURNAL OF PHYSICAL CHEMISTRY B, 121, DOI: 10.1021/acs.jpcb.7b02543