Theoretical and Computational Biochemistry

Theoretical and Computational Biochemistry

The TCB Group develops research in computational and theoretical sciences and is focused on 4 main lines of research - enzymatic catalysis, drug discovery, nanotechnology and crude oil desulfurization.

Our success in unraveling enzymatic mechanisms has granted us the recognition of the international scientific community and we have been invited to numerous plenary talks. In an effort to bridge fundamental and applied research, the group is also collaborating with several major companies in drug development, such as Bial, in order to develop different inhibitors for different enzymes. We have devised a protocol for drug discovery, which is granting us with major successes in the area of designing drugs.

Regarding projects with environmental impact, we are improving/accelerating the process of crude oil desulfurization, making it cleaner and less expensive, through the use of new, tailor-made enzymatic biocatalysts. Theoretical models have been developed to correlate amino acid sequence patterns with the formation of alpha-helix motifs and protein function. In parallel we conducted reactivity studies of chemical molecules that are important in biological processes.
The innovative approaches used to address these topics are internationally recognized and are the basis of several pieces of software used world-wide, as VMD (Visual Molecular Dynamics) plug-ins. These plug-ins are related to molecular docking, virtual screening and computational mutagenesis, all of them invaluable methodologies in Drug Discovery.

In 2013-2017 the TCB group has published 151 papers in WoS journals with 992 citations as well as 4 books/book chapters, 4 computer softwares with novel algorithms; supervised 15 PhD and 13 MSc theses; participated in 1 international project and 15 national projects (9 as PI), with an approximate total funding of 1.1M€.

TCB Research Labs
Recent publications
Listyarini, RV; Gesto, DS; Paiva, P; Ramos, MJ; Fernandes, PA. 2019. Benchmark of Density Functionals for the Calculation of the Redox Potential of Fe3+/Fe2+ Within Protein Coordination Shells. Frontiers in Chemistry, 7, DOI: 10.3389/fchem.2019.00391
Moreira, CDD; Ramos, MJRN; Fernandes, PMAA. 2019. Glutamine synthetase structure-catalysis relationship-Recent advances and applications. Wiley Interdisciplinary Reviews-Computational Molecular Science, 9, DOI: 10.1002/wcms.1399
Calixto, AR; Ramos, MJ; Fernandes, PA. 2019. Conformational diversity induces nanosecond-timescale chemical disorder in the HIV-1 protease reaction pathway. Chemical Science, 10, DOI: 10.1039/c9sc01464k
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