I would like to thank the Organising Committee of the VII AEICBAS Biomedical Congress (2019, March 17th) for the invitation to share my experience as a biochemist.
Is the 5,10methylenetetrahydrofolate cofactor synthesized through a non-enzymatic or enzymatic mechanism?
Fernandes, H. S., Sousa, S. F., and Cerqueira, N. M. F. S. A.
Last Saturday (November 17th), I was presenting some of the software that we have developed at BioSIM research group to improve the way some chemical concepts are taught to our students.
VMD extensions, such as VMD Magazine, ToolBar, Protein Wars, and VMD Store were presented during the “VII Encontro da Divisão de Ensino e Divulgação da Química” conference. During the presentation, the software features were presented and were showed how these extensions can be used to engage young students to learn chemistry in a more pleasant and clear manner.
Moreover, the BioSIM Augmented Reality technology was presented for the first time, and it allows an easy and costless way to see molecules using augmented reality. See the video below:
On September 28-29, I was presenting my recently published work at the UCIBIO Annual Meeting in Lisbon (FCT-NOVA).
The catalytic mechanism of Serine Hydroxymethyltransferase: a drug target against Malaria
Henrique S. Fernandes, M. J. Ramos, Sérgio F. Sousa, and N. M. F. S. A. Cerqueira
Henrique Silva Fernandes, Maria João Ramos, and Nuno M.F.S.A. Cerqueira
Published on 18th September 2018
Journal: ACS Catalysis
Serine Hydroxymethyltransferase (SHMT) is an important drug target to fight malaria – one of the most devastating infectious diseases that accounted in 2016 with 216 million new cases and almost 450 thousand deaths. In this paper, computational studies were carried out to unveil the catalytic mechanism of SHMT using QM/MM methodologies. This enzyme is responsible for the extraordinary cyclisation of a tetrahydrofolate (THF) into 5,10-methylene-THF. This process is catalyzed by a pyridoxal-5’-phosphate (PLP) cofactor that binds L-serine and from which one molecule of L-glycine is produced. The results show that the catalytic process takes place in eight sequential steps that involve an α-elimination, the cyclization of the 5-hydroxymethyl-THF intermediate into 5,10-methylene-THF and the protonation of the quinonoid intermediate. According to the calculated energetic profile, the rate-limiting step of the full mechanism is the elimination of the hydroxymethyl group, from which results a formaldehyde intermediate that then becomes covalently bonded to the THF cofactor. The calculated barrier (DLPNO-CCSD(T)/CBS:ff99SB) for the rate-limiting step (18.0 kcal/mol) agrees very well with the experimental kinetic results (15.7-16.2 kcal/mol). The results also highlight the key role played by Glu57 during the full catalytic process and particularly in the first step of the mechanism that requires an anionic Glu57, contrasting with some proposals available in the literature for this step. It was also concluded that the cyclisation of THF must take place in the enzyme, rather than in solution as it has been proposed also in the past. All of these results together provide new knowledge and insight on the catalytic mechanism of SHMT that now can be used to develop new inhibitors targeting SHMT and therefore new anti-malaria drugs.
Utilização de software na simulação molecular
Nuno Cerqueira, Sérgio Sousa, Henrique Fernandes e Carla Teixeira- Investigadores do DQB-FCUP
Conferência de especialidade
Dia 9 de Julho de 2018, 14h30
Auditório Grande do Centro Cultural Vila Flor
Maria João Ramos, Pedro Alexandrino Fernandes e Henrique Fernandes – Departamento de Química e Bioquímica da Faculdade de Ciências da Universidade do Porto
Esta conferência de especialidade será dividida em três partes. Numa primeira palestra, eu próprio apresentarei alguns dos recursos digitais que temos vindo a desenvolver para o ensino da química, que permitem levar as Moléculas Magníficas para a sala de aula, no sentido de não só facilitar o processo de aprendizagem, mas também, e fundamentalmente, para despertar nos estudantes o fascínio pela química e pela ciência. Numa segunda palestra, o nosso convidado Henrique Fernandes (estudante de doutoramento na Univ. do Porto) fará uma apresentação sobre um conjunto de Moléculas Magníficas específicas, mostrando a sua explicando o seu papel na nossa vida. Por fim, numa terceira e última palestra, a Prof.a Maria João Ramos apresentará a história da iniciativa Moléculas Magníficas, o seu nascimento, as várias iniciativas de disseminação que têm vindo a ser feitas, as várias exposições, e os projetos futuros.
Entre as palestras terão lugar momentos de debate com a assembleia de participantes.
The molUP plugin, developed by Nuno Sousa Cerqueira and colleagues and described on page 1344, overcomes some of the most common problems in computational chemistry concerning the analysis of big data. MolUP was developed for use in the analysis of quantum chemistry (QM), QM/MM (molecular mechanics), and QM/QM calculations, molecular dynamics (MD) simulations, as well as the preparation of input files. MolUP also provides new tools to analyze and visualize existing computational chemistry information in a more userfriendly way that simplifies the current complex and time‐demanding practices used in the field. (DOI: 10.1002/jcc.25189)
New Software Applications for Biomolecular Simulations: Applications to Chemistry and Biochemistry.
CHEMTECH DQB – Chemistry Technology Events at DQB – 2018
March 8th, 2018 – Departamento de Química e Bioquímica da Faculdade de Ciências da Universidade do Porto
Descrição da Atividade
Realizou-se no Departamento de Química e Bioquímica da Faculdade de Ciências da Universidade do Porto uma mini feira de ciência onde se mostraram os softwares desenvolvidos no grupo de Bioquímica Teórica e Computacional. Os softwares são todos eles extensões para o VMD (Visual Molecular Dynamics) um visualizador molecular gratuito desenvolvido pela Universidade Illinois.
Os participantes tiveram a oportunidade de falar com os desenvolvedores e experimentar os softwares, que sendo gratuitos podem ser mais tarde instalados e usados por cada um dos participantes.
Fica aqui o folheto que foi distribuído na sessão demonstrativa: Download
E ainda algumas fotografias do evento:
André F. Pina
Carla S. S. Teixeira
Henrique S. Fernandes
Juliana F. Rocha
Nuno M. F. S. A. Cerqueira
Sérgio F. Sousa
Henrique Silva Fernandes, Maria João Ramos, and Nuno M.F.S.A. Cerqueira
The notable advances obtained by computational (bio)chemistry provided its widespread use in many areas of science, in particular, in the study of reaction mechanisms. These studies involve a huge number of complex calculations, which are often carried out using the Gaussian suite of programs. The preparation of input files and the analysis of the output files are not easy tasks and often involve laborious and complex steps. Taking this into account, we developed molUP: a VMD plugin that offers a complete set of tools that enhance the preparation of QM and ONIOM (QM/MM, QM/QM, and QM/QM/MM) calculations. The starting structures for these calculations can be imported from different chemical formats. A set of tools is available to help the user to examine or modify any geometry parameter. This includes the definition of layers in ONIOM calculations, choosing fixed atoms during geometry optimizations, the recalculation or adjustment of the atomic charges, performing SCANs or IRC calculations, etc. molUP also extracts the geometries from the output files as well as the energies of each of them. All of these tasks are performed in an interactive GUI that is extremely helpful for the user. MolUP was developed to be easy to handle by inexperienced users, but simultaneously to be a fast and flexible graphical interface to allow the advanced users to take full advantage of this plugin. The program is available, free of charges, for macOS, Linux, and Windows at the PortoBioComp page https://www.fc.up.pt/PortoBioComp/database/doku.php?id=molup.