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Protein synthesis and protein degradation are two universal complementary processes, permanently occurring in a living cell. Protein backbones are very stable in water at neutral pH and room temperature. The half-life of a peptide bond under normal conditions can range from 7 years to 600 years, even higher for peptides protected by modified terminus or within the protein interior.But there is a group of enzymes, the proteases, whose catalytic function is to hydrolyse peptide bonds with very high efficiency.

The view of proteases has come a long way since P. A. Levene reported his studies on "The Cleavage Products of Proteases" in the first issue of The Journal of Biological Chemistry published October 1, 1905. Today, after more than 100 years and more than 350,000 articles on these enzymes in the scientific literature, proteases remain at the cutting edge of biological research.

Project Leader: Dr. Katarzyna Świderek

Proteases are classified based on their mode of action and biocatalytic mechanisms. Natural and modified commercial proteases are produced with applications in detergents, leather, food processing, and medicine. They are also used as biocatalysts in organic synthesis. Proteases are present in all organisms where they participate in most aspects of cell nutrition, physiology, regulation, and in microbial pathogenesis.

Depending on their site of action, proteases are categorized into two major groups: exoproteases and endoproteases. Further classification relies on the distinct arrangement of functional groups present at the active site of the enzyme. Non-metal proteases are subdivided into five different subgroups: cysteine, aspartate, serine, glutamic acid and threonine proteases. The physiological roles of proteases are very diverse, participating in a wide range of molecular and cellular activities, including from digestive functions, the removal of damaged proteins, and protein maturation to the precise processing of regulatory proteins.

Just Published:

N. Serrano-Aparicio, S. Ferrer, K. Świderek* "Covalent Inhibition of the Human 20S Proteasome with Homobelactosin C Inquired by QM/MM Studies" Pharmaceuticals 15, 531, (2022). doi:10.3390/ph15050531

M. À. Galmés, A. R. Nodling, K. He, L. Y. P. Luk*, K. Świderek*, V. Moliner* "Computational design of an amidase by combining the best electrostatic features of two promiscuous hydrolases" Chem. Sci. just accepted (2022) doi:10.1039/d2sc00778a

S. Martí, K. Arafet, A. Lodola, A. J. Mulholland, K. Świderek*, V. Moliner* "Impact of Warhead Modulations on the Covalent Inhibition of SARS-CoV-2 Mpro Explored by QM/MM Simulations" ACS Catal. 12, 1, 698-708 (2022) doi: 10.1021/acscatal.1c04661

A. R. Nödling, N. Santi, R. Castillo, M. Lipka-Lloyd, Y. Jin, L. C. Morrill, K. Świderek,* V. Moliner*, L. Y. P. Luk* "The role of streptavidin and its variants in catalysis by biotinylated secondary amines" Org. Biomol. Chem. 19, 10424-10431, (2021). doi:10.1039/D1OB01947C

Back to BioComp web >>

26/12/2021

S. Martí, K. Arafet, A. Lodola, A. J. Mulholland, K. Świderek*, V. Moliner* ACS Catal. 12, 1, 698-708 (2022) doi: 10.1021/acscatal.1c04661

06/09/2021

H.T.H. Chan, M.A. Moesser, R.K. Walters, T.R. Malla, R.M. Twidale, T. John, H.M. Deeks, T. Johnston-Wood, V. Mikhailov, R.B. Sessions, W. Dawson, E. Saleh, P. Lukacik, C. Strain-Damerell, C.D. Owen, T. Nakajima, K. Świderek, A. Lodola, V. Moliner, D.R. Glowacki, J. Spencer, M.A.A. Walsh, C.J. Schofield, L. Genovese, D.K. Shoemark, A.J. Mulholland, F. Duarte, G.M. Morris Chem. Sci. 12, 13686-13703 (2021) doi:10.1039/D1SC03628A

27/11/2020

K. Arafet, N. Serrano-Aparicio A. Lodola A. Mulholland, F. V. González, K. Świderek*, V. Moliner* Rxiv Chem. Sci. 12, 1433-1444 (2021) Chem Preprint Doi: 10.26434/chemrxiv.12941819.v1

25/06/2020

K. Świderek*, V. Moliner* Chem. Sci. 11, 10626-10630 (2020) Chem Rxiv Preprint Doi: 10.26434/Chemrxiv.12283967.V1 2020 Chemical Science HOT Article Collection And Celebrating 10 Years Of Chemical Science

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Protein synthesis and protein degradation are two universal complementary processes, permanently occurring in a living cell. Protein backbones are very stable in water at neutral pH and room temperature.

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The BioComp group at Universitat Jaume I leaded by Prof. Vicent Moliner and Dr. Sergio Marti is devoted to the computational description of catalysis phenomena in biological systems, mostly enzyme catalyzed processes. For this purpose, theories, methods and techniques of theoretical and computational chemistry are developed, implemented and used. Computational algorithms and protocols, based on hybrid QM/MM potentials, are created and this new knowledge is exploited in designing new materials with properties to be used in biomedicine and biotechnology. In particular, these applications are focused on elucidating enzyme reaction mechanisms including fundamental new quantum and dynamical perspectives, to design new pharmacological agents to inhibit enzyme activity, or new catalysts mimicking the catalytic efficiency and features of natural enzymes.

LATEST PUBLICATIONS:

A. R. Nödling, N. Santi, R. Castillo, M. Lipka-Lloyd, Y. Jin, L. C. Morrill, K. Świderek,* V. Moliner*, L. Y. P. Luk* "The role of streptavidin and its variants in catalysis by biotinylated secondary amines" Org. Biomol. Chem. 19, 10424-10431, (2021). doi:10.1039/D1OB01947C

J.R.A. Silva, J. Urban, E. Araújo, J. Lameira, V. Moliner, C.N. Alves"Exploring the Catalytic Mechanism of the RNA Cap Modification by nsp16-nsp10 Complex of SARS-CoV-2 through a QM/MM Approach" Int. J. Mol. Sci. 23, 300 (2022) doi:10.3390/ijms23010300

N. Serrano-Aparicio, V.Moliner*, K. Świderek* "On the Origin of the Different Reversible Characters of Salinosporamide A and Homosalinosporamide A in the Covalent Inhibition of the Human 20S Proteasome" ACS Catal. 11, 11806–11819, (2021) doi:10.1021/acscatal.1c02614

N. Serrano-Aparicio, K. Świderek*, I. Tuñón, V.Moliner*, J. Bertran "Theoretical Studies of the Self Cleavage Pistol Ribozyme Mechanism" Top Catal 1-12 (2021) doi:10.1007/s11244-021-01494-1

Special COVID-19 project:

K. Świderek, V. Moliner "Revealing the Molecular Mechanisms of Proteolysis of SARS-CoV-2 Mpro from QM/MM Computational Methods."
Chem. Sci. just accepted (2020) Chem Rxiv Preprint Doi: 10.26434/Chemrxiv.12283967.V1 This Article Is Part Of The Themed Collection: 2020 Chemical Science HOT Article Collection And Celebrating 10 Years Of Chemical Science, Featured On The Front Cover Issue 39, 2020.

K. Arafet, N. Serrano-Aparicio A. Lodola A. Mulholland, F. V. González, K. Świderek*, V. Moliner* "Mechanism of Inhibition of SARS-CoV-2 Mpro by N3 Peptidyl Michael Acceptor Explained by QM/MM Simulations and Design of New Derivatives with Tunable Chemical Reactivity." Chem. Sci. just accepted (2021) ChemRxiv Preprint doi: 10.26434/chemrxiv.12941819.v1

H.T.H. Chan, M.A. Moesser, R.K. Walters, T.R. Malla, R.M. Twidale, T. John, H.M. Deeks, T. Johnston-Wood, V. Mikhailov, R.B. Sessions, W. Dawson, E. Saleh, P. Lukacik, C. Strain-Damerell, C.D. Owen, T. Nakajima, K. Świderek, A. Lodola, V. Moliner, D.R. Glowacki, J. Spencer, M.A.A. Walsh, C.J. Schofield, L. Genovese, D.K. Shoemark, A.J. Mulholland, F. Duarte, G.M. Morris "Discovery of SARS-CoV-2 Mpro Peptide Inhibitors from Modelling Substrate and Ligand Binding" Chem. Sci. (2021) Accepted Manuscript doi:10.1039/D1SC03628A

S. Marti, K. Arafet, A. Lodola, A. Mulholland, K. Świderek*, V. Moliner* "Impact of warhead modulations on the covalent inhibition of SARS-CoV-2 Mpro explored by QM/MM simulations" ACS Catal. 12, 1, 698–708 (2022) doi: 10.1021/acscatal.1c04661 ChemRxiv Preprint Doi:10.33774/chemrxiv-2021-590p0

Go to BioComp StopProt project >>

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vicent, moliner, sergio, marti, computational

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Computational Biochemistry laboratory at UJI is focused on molecular simulations of enzymes catalyzed processes. Leaded by Vicent Moliner and Sergio Marti.

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Licenses: All visualizations, data, and articles produced by Our World in Data are open access under the Creative Commons BY license. You have permission to use, distribute, and reproduce these in any medium, provided the source and authors are credited. All the software and code that we write is open source and made available via GitHub under the permissive MIT license. All other material, including data produced by third parties and made available by Our World in Data, is subject to the license terms from the original third-party authors.

Please consult our full legal disclaimer.

Our World In Data is a project of the Global Change Data Lab, a registered charity in England and Wales (Charity Number 1186433).

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Research and data to make progress against the world's largest problems

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The hepatitis B virus (HBV) is one of the smallest human pathogens that infects liver cells chronically affecting ~250 million people globally. The breaking of the HBV capsid leads to the release of its genetic material into the host cell and therefore a key step in its infection. The capsid consists of hundreds of identical protein blocks. Using molecular dynamics simulations with NAMD we devised a mechanical stress to study the process of capsid disassembly in a simulation composed of millions of particles. Analyzing the resulting capsid cracks by VMD we show that the cracks mainly occur within a particular (hexameric) protein arrangements. More importantly, only a small subset of the capsid proteins are engaged in initiating the disassembly. The majority of such hot-spot residues are conserved through evolution, hinting at their importance in the viral infection process, probably by destabilizing the capsid to the right degree. Read more in the Beckman Institute press release and the published article in Proceedings of the National Academy of Sciences.

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TCBG Highlight: Cracking Open the Hepatitis B Virus

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The hepatitis B virus (HBV) is one of the smallest human pathogens that infects liver cells chronically affecting ~250 million people globally. The breaking of the HBV capsid leads to the release of its genetic material into the host cell and therefore a key step in its infection.

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This website provides an access to:

SwissDock, a web service to predict the molecular interactions that may occur between a target protein and a small molecule.

S3DB, a database of manually curated target and ligand structures, inspired by the Ligand-Protein Database.

Would you like to organize a workshop? Please let us know so that we can adjust the computing resources accordingly.

SwissDock is based on the docking software EADock DSS, whose algorithm consists of the following steps:

1. many binding modes are generated either in a box (local docking) or in the vicinity of all target cavities (blind docking).

2. simultaneously, their CHARMM energies are estimated on a grid.

3. the binding modes with the most favorable energies are evaluated with FACTS, and clustered.

4. the most favorable clusters can be visualized online and downloaded on your computer.

SwissDock and S3DB are developed by Aurélien Grosdidier, Vincent Zoete and Olivier Michielin, from the Molecular Modeling Group of the Swiss Institute of Bioinformatics in Lausanne, Switzerland.

Calculations are performed on the Vital-IT cluster ( status)

EADock and SwissDock have been funded by the FNS project grant #310030_130857 and the Swiss Institute of Bioinformatics

You can easily create direct links to the SwissDock submission form, preloaded with protein and ligand structures defined as URLs:

Inspect the source code of this page to see how easy it is !

If you use this webservice, please let us know and cite:

Feel free to check a list of selected papers who cites us

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This website provides an access to: SwissDock, a web service to predict the molecular interactions that may occur between a target protein and a small molecule. S3DB, a database of manually curated target and ligand structures, inspired by the Ligand-Protein Database. Would you like to organize a workshop?

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Network Parameters

EXAMPLE

MD Parameters

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As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are…