Workshop “Utilização de software na simulação molecular” – V Encontro Internacional da Casa das Ciências

Utilização de software na simulação molecular

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Nuno Cerqueira, Sérgio Sousa, Henrique Fernandes e Carla Teixeira- Investigadores do DQB-FCUP

As tecnologias de informação e comunicação são nos dias de hoje uma ferramenta apelativa para o ensino da química. Neste contexto, salientam-se os programas de computador utilizados em modelação molecular que permitem visualizar e interpretar vários fenómenos químicos e que são normalmente difíceis de lecionar ou entendidos pelos alunos. Este workshop tem por objetivo a apresentação de vários programas de modelação molecular (como por exemplo Avogadro ou VMD) que permitem a visualização e edição de estruturas moleculares, bem como o cálculo de propriedades químicas de algumas moléculas. Todas as ferramentas apresentadas serão de acesso livre e por isso poderão ser instaladas e usadas pelos professores e alunos sem qualquer custo. Os exemplos abordados poderão ser mais tarde utilizados na sala de aula e permitir a construção de um ambiente de aprendizagem mais dinâmico e interativo, tornando o conteúdo lecionado mais estimulante e elucidativo para os alunos.
Informação aos formandos: os participantes deverão fazer-se acompanhar dos seus portáteis.

Moléculas Magníficas – V Encontro Internacional da Casa das Ciências 2018

Conferência de especialidade

Dia 9 de Julho de 2018, 14h30

Auditório Grande do Centro Cultural Vila Flor

Moléculas Magníficas

Maria João Ramos, Pedro Alexandrino Fernandes e Henrique Fernandes – Departamento de Química e Bioquímica da Faculdade de Ciências da Universidade do Porto

Todas as moléculas são magníficas, mas algumas são mais magníficas que outras. Nesta conferência vamos apresentar algumas das moléculas incrivelmente complexas que comandam a nossa biologia, falando do seu papel, da sua função e do que é que as faz tão magníficas e fascinantes. Vamos ainda mostrá-las de uma forma artística, recorrendo às mais modernas tecnologias gráficas, para criar obras de arte a partir da ciência e do conhecimento.
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.

Uma tarde FQ! #5ei_cdc

Uma publicação partilhada por fisicaequimica.com (@trap_photon) a

Photos

molUP is cover of the Journal of Computational Chemistry 39(19)

Cover

First published: 10 June 2018 | https://doi.org/10.1002/jcc.25372

Abstract

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)

Feira de Ciência – New Software Applications for Biomolecular Simulations

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:

Organização

André F. Pina
Carla S. S. Teixeira
Henrique S. Fernandes
Juliana F. Rocha
Nuno M. F. S. A. Cerqueira
Sérgio F. Sousa

molUP: a VMD plugin to handle QM and ONIOM calculations using the Gaussian software

Henrique Silva Fernandes, Maria João Ramos, and Nuno M.F.S.A. Cerqueira

Published on 21st February 2018
DOI: http://dx.doi.org/10.1002/jcc.25189 | Download citation

Abstract

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.

Volta ao Conhecimento – 79ª Volta a Portugal em Bicicleta

No dia 13 de agosto de 2017, o grupo de Bioquímica Teórica e Computacional esteve representado na Feira da 79ª Volta a Portugal em Bicicleta, no âmbito do projeto Volta ao Conhecimento promovido pelo Ministério da Ciência, Tecnologia e Ensino Superior.

O stand esteve montado junto à meta da 8ª etapa em Oliveira de Azeméis e contou com a participação de vários cidadãos que se deslocaram para assistir ao término de mais uma etapa da Volta.

Optámos por montar umm stand muito interativo com uma máquina de jogos educativa, o ProteinWars, cujo o objetivo é mostrar de que forma estudamos as proteínas e as moléculas para desenvolver novos fármacos.

Além disso, um segundo computador com um joystick acoplado permitiu aos participantes visualizarem moléculas e interagirem com os átomos em simulações moleculares.

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Página da Volta ao Conhecimento

The Catalytic Mechanism of the Pyridoxal-5′-phosphate-Dependent Enzyme, Histidine Decarboxylase: A Computational Study

Henrique Silva Fernandes, Maria João Ramos, and Nuno M.F.S.A. Cerqueira

Published on June 14th 2017
DOI: http://dx.doi.org/10.1002/chem.201701375 | Download citation

Abstract

The catalytic mechanism of histidine decarboxylase (HDC), a pyridoxal-5′-phosphate (PLP)-dependent enzyme, was studied by using a computational QM/MM approach following the scheme M06-2X/6–311++G(3df,2pd):Amber. The reaction involves two sequential steps: the decarboxylation of l-histidine and the protonation of the generated intermediate from which results histamine. The rate-limiting step is the first one (ΔG=17.6 kcal mol−1; ΔGr=13.7 kcal mol−1) and agrees closely with the available experimental kcat (1.73 s−1), which corresponds to an activation barrier of 17.9 kcal mol−1. In contrast, the second step is very fast (ΔG=1.9 kcal mol−1) and exergonic (ΔGr=−33.2 kcal mol−1). Our results agree with the available experimental data and allow us to explain the role played by several active site residues that are considered relevant according to site-directed mutagenesis studies, namely Tyr334B, Asp273A, Lys305A, and Ser354B. These results can provide insights regarding the catalytic mechanism of other enzymes belonging to family II of PLP-dependent decarboxylases.

Nanostructures for Cancer Therapy – Elsevier

Editors: Alexandru Grumezescu Anton Ficai
eBook ISBN: 9780323461504
Hardcover ISBN: 9780323461443
Imprint: Elsevier
Published Date: 14th April 2017
Page Count: 920

Nanostructures for Cancer Therapy discusses the available preclinical and clinical nanoparticle technology platforms and their impact on cancer therapy, including current trends and developments in the use of nanostructured materials in chemotherapy and chemotherapeutics.

In particular, coverage is given to the applications of gold nanoparticles and quantum dots in cancer therapies. In addition to the multifunctional nanomaterials involved in the treatment of cancer, other topics covered include nanocomposites that can target tumoral cells and the release of antitumoral therapeutic agents.

The book is an up-to-date overview that covers the inorganic and organic nanostructures involved in the diagnostics and treatment of cancer.

Chapter 24 – Cancer Therapies Based on Enzymatic Amino Acid Depletion

Carla Teixeira*, Henrique Fernandes*, P. A. Fernandes, M. J. Ramos and Nuno M. F. S. A. Cerqueira (* contributed equally to this work)

Buy on Elsevier | Buy on Amazon | Available on iTunes | Preview

Image 1.jpg

 

Abstract

A growing understanding of tumor biology has allowed the identification of various cellular characteristics that are more frequently associated with cancer cells than with normal cells. These findings have prompted the development of new therapeutics specifically designed to exploit these differences. In this context, the amino acid depriving enzymes have shown very promising results and proven to be active and very specific against various types of cancers. These therapies involve the depletion of specific amino acids in the bloodstream that cannot be synthesized by tumor cells. This happens because these cells often have a defecting enzymatic armamentarium and therefore rely on external supply for those amino acids. Decreasing the concentration of certain amino acids in blood has thus been shown to impair the development or even destroy tumor cells. Normal cells remain unaltered since they are less demanding and/or can synthesize these compounds in sufficient amounts by other mechanisms.

In this chapter, the structure, function, catalytic mechanism and therapeutic application of some amino acid depriving enzymes will be reviewed. Particular attention will be given to enzymes that have potential or are currently used in the treatment of several types of cancer, namely: (1) l-asparaginase used for the treatment of acute lymphoblastic leukemia; (2) l-arginase and l-arginine deiminase that are used in the therapy of hepatocellular carcinomas and melanomas, two diseases that account annually with approximately 1 million of new cases and for which there is currently no efficacious treatment; and (3) l-Methioninase with potential to be used in the treatment of breast, colon, lung, and renal cancers.

Keywords

  • amino acid deprivation;
  • heterologous enzymes;
  • tumor;
  • cancer;
  • catalytic mechanism;
  • asparaginase;
  • methioninase;
  • arginase;
  • arginine deaminase

Poster | 5º Encontro Português de Jovens Químicos (PYCheM) and 1st European Young Chemists Meeting

Centro Cultural Vila Flor, Guimarães

2016, 22th to 24th April

Poster: “Computational studies addressed to the catalytic mechanism of Histidine Decarboxylase”

Henrique S. Fernandes (1), Maria João Ramos, Nuno M. F. S. A. Cerqueira (1)

(1) UCIBIO/REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre s/n, 4169-007 Porto, PT

Mammalian histidine decarboxylase (mHDC) is an enzyme that requires pyridoxal-5′-phosphate (PLP) as a cofactor [1-3]. mHDC belongs to the group II of PLP-dependent decarboxylases together with L-DOPA and glutamate decarboxylases, and catalyses the L-histidine decarboxylation from which results histamine.

Histamine plays a key role in several biological events such as immune response, gastric system modulation and as a neurotransmitter in the nervous system. Several inhibitors for histamine action have been studied in order to treat some diseases such as atopic dermatitis, allergies, and cancer.

mHDC has been studied for a long time, but only in 2012 Komori’s [2] group was able to determine the X-ray structure of the enzyme and revealed the active site environment. Till date, only hypothesis about the catalytic mechanism of mHDC were available and based on homology models (that propose a different active site configuration).

In this work, we studied the catalytic mechanism of mHDC by computational approaches using the recent X-ray structure of mHDC (PDB code: 4E1O [4]) and a QM/MM methodology.

The results have shown that mHDC catalyses the reaction in a two-step type of mechanism. The first step involves a decarboxylation that is followed by the formation of a stable carbanion. In the second step, the carbanion is protonated by a base from which results histamine.

[1] Ngo, H. P., Cerqueira, N. M., Kim, J. K., Hong, M. K., Fernandes, P. A., Ramos, M. J., and Kang, L. W., Acta crystallographica. Section D, Biological crystallography 2014, 70, 596-606

[2] Oliveira, Eduardo F.; Cerqueira, Nuno M. F. S. A.; Fernandes, Pedro A. and Ramos, M.J., Journal of the American Chemical Society 2011, 133, 15496-15505

[3] Cerqueira, N. M. F. S. A.; Fernandes, P. A.; Ramos, M. J., Journal of Chemical Theory and Computation 2011, 7, 1356-1368

[4] Komori, H., Nitta, Y., Ueno, H., and Higuchi, Y., Acta Crystallogr Sect F Struct Biol Cryst Commun 2012, 68, 675-677