The Biofilms Structural Database

Check our recent publication about “The Biofilms Structural Database”, a database devoted to the proteins involved in the biofilms’ formation.


The Biofilms Structural Database (BSD) is a collection of structural, mutagenesis, kinetics, and inhibition data to understand the processes involved in biofilm formation. Presently, it includes curated information on 425 structures of proteins and enzymes involved in biofilm formation and development for 42 different bacteria. It is available at

Authors: Magalhães RP, Vieira TF, Fernandes HS, Melo A, Simões M, and Sousa SF

Modelling Enzymatic Mechanisms with QM/MM Approaches: Current Status and Future Challenges

Our recent review about studying enzymatic mechanisms using QM/MM mythologies has just been accepted on Israel Journal of Chemistry.


Quantum mechanics/molecular mechanics (QM/MM) methods are presently a well‐established alternative for the study of enzymatic reaction mechanisms. They enable the description of a small part of the enzyme, where reactions take place through QM, while the majority of the thousands of atoms that comprise these biomolecules are handled through MM. While different “flavors” and variations in the QM/MM field exist, this review will focus more on the application of the ONIOM methodology, presenting a fresh perspective on the application of this popular method in light of the growth in computational power and level of sophistication of the different methodologies that it can combine. In addition to a brief presentation of the basic principles behind these methods, this review will discuss different examples of applicability, common choices, practical considerations, and main problems involved, stemming from our experience in this field. Finally, a reflection on the future challenges for the next decade in the QM/MM modeling of enzymatic mechanisms is presented.

Authors: Magalhães RP, Fernandes HS, and Sousa SF

VMD Store – a VMD Plugin to Browse, Discover, and Install VMD Extensions

Henrique Silva Fernandes, Sérgio F. Sousa, and Nuno M.F.S.A. Cerqueira

Published on 21st October 2019
Journal: Journal of Chemical Information and Modeling | Download citation


Herein we present the VMD Store, an open-source VMD plugin that simplifies the way how users browse, discover, install, update, and uninstall extensions for the Visual Molecular Dynamics (VMD) software. The VMD Store obtains data about all the indexed VMD extensions hosted on GitHub and presents a one-click mechanism to install and configure VMD extensions. This plugin arises in an attempt to aggregate all VMD extensions in a single platform. The VMD Store is available, free of charge, for Windows, macOS, and Linux at, and requires VMD 1.9.3 (or later).

The 19th YSF and 44th FEBS conferences

I was at the 19th YSF and 44th FEBS conferences, in Krakow – Poland, during the last week (July 3rd to 11th) presenting my work about “Enhancing the catalytic power of Serine Hydroxymethyltransferase to produce commercially valuable compounds”. It was an excellent congress where I got some new ideas for the future. Thank you

Formation of Unstable and very Reactive Chemical Species Catalyzed by Metalloenzymes: A Mechanistic Overview

Henrique S. Fernandes, Sérgio F. Sousa, and Nuno M.F.S.A. Cerqueira

Journal: Molecules


Nature has tailored a wide range of metalloenzymes that play a vast array of functions in all living organisms and from which their survival and evolution depends on. These enzymes catalyze some of the most important biological processes in nature, such as photosynthesis, respiration, water oxidation, molecular oxygen reduction, and nitrogen fixation. They are also among the most proficient catalysts in terms of their activity, selectivity, and ability to operate at mild conditions of temperature, pH, and pressure. In the absence of these enzymes, these reactions would proceed very slowly, if at all, suggesting that these enzymes made the way for the emergence of life as we know today. In this review, the structure and catalytic mechanism of a selection of diverse metalloenzymes that are involved in the production of highly reactive and unstable species, such as hydroxide anions, hydrides, radical species, and superoxide molecules are analyzed. The formation of such reaction intermediates is very difficult to occur under biological conditions and only a rationalized selection of a particular metal ion, coordinated to a very specific group of ligands, and immersed in specific proteins allows these reactions to proceed. Interestingly, different metal coordination spheres can be used to produce the same reactive and unstable species, although through a different chemistry. A selection of hand-picked examples of different metalloenzymes illustrating this diversity is provided and the participation of different metal ions in similar reactions (but involving different mechanism) is discussed.

Poster at EJIBCE 2018

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.

Desenvolvimento de Software com Aplicação no Ensino Em Química e Biologia – VII Encontro da Divisão de Ensino e Divulgação da Química

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:

The catalytic mechanism of the Serine Hydroxymethyltransferase – a computational ONIOM QM/MM study

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

Published on 18th September 2018
Journal: ACS Catalysis | Download citation


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.