Expertise

The activity of the research group in Chemiformatics & Nutrition focuses on using computational tools to: (1) predict which natural molecules have one specific bioactivity; (2) find new uses for specific molecules (e.g., valorization of by-products by finding new uses for molecules that are present on them). Our results can be used either to design functional foods/nutraceutics for specific risk population's groups (e.g., people that have the risk to become diabetic) or to develop new molecular cosmetics products or to find/design/improve drugs. Moreover, our group is able to experimentally confirm the predicted bioactivity by means of in vitro, in vivo and ex vivo experiments. These experiments are performed at the self group facilities.

Working topics:

(1) Finding natural molecules with anti-inflammatory activity

• Identification of human IKK-2 inhibitors of natural origin (part I): modeling of the IKK-2 kinase domain, virtual screening and activity assays. Sala E, Guasch L, Iwaszkiewicz J, Mulero M, Salvadó MJ, Pinent M, Zoete V, Grosdidier A, Garcia-Vallvé S, Michielin O, Pujadas G. PLoS One. 2011 Feb 24;6(2):e16903
• Identification of human IKK-2 inhibitors of natural origin (Part II): in Silico prediction of IKK-2 inhibitors in natural extracts with known anti-inflammatory activity. Sala E, Guasch L, Iwaszkiewicz J, Mulero M, Salvadó MJ, Bladé C, Ceballos M, Valls C, Zoete V, Grosdidier A, Garcia-Vallvé S, Michielin O, Pujadas G. Eur J Med Chem. 2011 Dec;46(12):6098-103
• Anti-Inflammatory and Immunomodulatory Effects of the Grifola frondosa Natural Compound o-Orsellinaldehyde on LPS-Challenged Murine Primary Glial Cells. Roles of NF-κβ and MAPK. Tomas-Hernandez S, Blanco J, Garcia-Vallvé S, Pujadas G, Ojeda-Montes MJ, Gimeno A, Arola L, Minghetti L, Beltrán-Debón R, Mulero M. Pharmaceutics. 2021 May 28;13(6):806. doi: 10.3390/pharmaceutics13060806.
• Anti-inflammatory and Proapoptotic Properties of the Natural Compound o-Orsellinaldehyde. Tomas-Hernandez S, Garcia-Vallvé S, Pujadas G, Valls C, Ojeda-Montes MJ, Gimeno A, Cereto-Massagué A, Roca-Martinez J, Suárez M, Arola L, Blanco J, Mulero M, Beltran-Debón R. J Agric Food Chem. 2018 Oct 24;66(42):10952-10963. doi: 10.1021/acs.jafc.8b00782.

(2) Finding natural molecules with anti-diabetic activity

• Identification of novel human dipeptidyl peptidase-IV inhibitors of natural origin (part I): virtual screening and activity assays. Guasch L, Ojeda MJ, González-Abuín N, Sala E, Cereto-Massagué A, Mulero M, Valls C, Pinent M, Ardévol A, Garcia-Vallvé S, Pujadas G. PLoS One. 2012;7(9):e44971
• Identification of novel human dipeptidyl peptidase-IV inhibitors of natural origin (Part II): in silico prediction in antidiabetic extracts. Guasch L, Sala E, Ojeda MJ, Valls C, Bladé C, Mulero M, Blay M, Ardévol A, Garcia-Vallvé S, Pujadas G. PLoS One. 2012;7(9):e44972
• Identification of PPARgamma partial agonists of natural origin (I): development of a virtual screening procedure and in vitro validation. Guasch L, Sala E, Castell-Auví A, Cedó L, Liedl KR, Wolber G, Muehlbacher M, Mulero M, Pinent M, Ardévol A, Valls C, Pujadas G, Garcia-Vallvé S. PLoS One. 2012;7(11):e50816
• Identification of PPARgamma partial agonists of natural origin (II): in silico prediction in natural extracts with known antidiabetic activity. Guasch L, Sala E, Mulero M, Valls C, Salvadó MJ, Pujadas G, Garcia-Vallvé S. PLoS One. 2013;8(2):e55889.
• Discovery of Natural Products that Modulate the Activity of PPARgamma: A Source for New Antidiabetics. Garcia-Vallve S, Guasch L, Mulero M. Foodinformatics Applications of Chemical Information to Food Chemistry, 151-176. Editors: Karina Martinez-Mayorga and José Luis Medina-Franco. Springer 2014
• DPP-IV, An Important Target for Antidiabetic Functional Food Design. Ojeda MJ, Cereto-Massagué A, Valls C, Pujadas G. Foodinformatics Applications of Chemical Information to Food Chemistry, 177-212. Editors: Karina Martinez-Mayorga and José Luis Medina-Franco. Springer 2014

(3) Finding matrix metalloproteinase (MMP) inhibitors

• Identification of Broad-Spectrum MMP Inhibitors by Virtual Screening. Gimeno A, Cuffaro D, Nuti E, Ojeda-Montes MJ, Beltrán-Debón R, Mulero M, Rossello A, Pujadas G, Garcia-Vallvé S. . Molecules. 2021 Jul 28;26(15):4553. doi: 10.3390/molecules26154553.
• Understanding the variability of the S1' pocket to improve matrix metalloproteinase inhibitor selectivity profiles. Gimeno A, Beltrán-Debón R, Mulero M, Pujadas G, Garcia-Vallvé S. Drug Discov Today. 2020 Jan;25(1):38-57. doi: 10.1016/j.drudis.2019.07.013.

• Cuffaro D, Gimeno A, Bernardoni BL, Di Leo R, Pujadas G, Garcia-Vallvé S, Nencetti S, Rossello A, Nuti E. Identification of N-Acyl Hydrazones as New Non-Zinc-Binding MMP-13 Inhibitors by Structure-Based Virtual Screening Studies and Chemical Optimization. Int J Mol Sci. 2023 Jul 4;24(13):11098. doi: 10.3390/ijms241311098.

(4) Development of methodologies/computational tools for improving the prediction of the bioactivity of small molecules

• DecoyFinder: an easy-to-use python GUI application for building target-specific decoy sets. Cereto-Massagué A, Guasch L, Valls C, Mulero M, Pujadas G, Garcia-Vallvé S. Bioinformatics. 2012 Jun 15;28(12):1661-2
• The good, the bad and the dubious: VHELIBS, a validation helper for ligands and binding sites. Cereto-Massagué A, Ojeda MJ, Joosten RP, Valls C, Mulero M, Salvado MJ, Arola-Arnal A, Arola L, Garcia-Vallvé S, Pujadas G. J Cheminform. 2013 Jul 29;5(1):36. doi: 10.1186/1758-2946-5-36.

(5) Development of methodologies/computational tools for predicting new uses for existing drugs or molecules that are abundant in by-products of natural origin

• Molecular fingerprint similarity search in virtual screening. Cereto-Massagué A, Ojeda MJ, Valls C, Mulero M, Garcia-Vallvé S, Pujadas G. Methods. 2015 Jan;71:58-63.
• Tools for in silico target fishing. Cereto-Massagué A, Ojeda MJ, Valls C, Mulero M, Pujadas G, Garcia-Vallve S. Methods. 2015 Jan;71:98-103.

(6) Prediction of new inhibitors of the main protease of SARS-CoV-2

• Prediction of Novel Inhibitors of the Main Protease (M-pro) of SARS-CoV-2 through Consensus Docking and Drug Reposition. Gimeno A, Mestres-Truyol J, Ojeda-Montes MJ, Macip G, Saldivar-Espinoza B, Cereto-Massagué A, Pujadas G, Garcia-Vallvé S. Int J Mol Sci. 2020 May 27;21(11):3793. doi: 10.3390/ijms21113793.

• A Review of the Current Landscape of SARS-CoV-2 Main Protease Inhibitors: Have We Hit the Bullseye Yet? Macip G, Garcia-Segura P, Mestres-Truyol J, Saldivar-Espinoza B, Pujadas G, Garcia-Vallvé S. Int. J. Mol. Sci. 2022, 23, 259. https://doi.org/10.3390/ijms23010259

• Haste makes waste: A critical review of docking-based virtual screening in drug repurposing for SARS-CoV-2 main protease (M-pro) inhibition. Macip G, Garcia-Segura P, Mestres-Truyol J, Saldivar-Espinoza B, Ojeda-Montes MJ, Gimeno A, Cereto-Massagué A, Garcia-Vallvé S, Pujadas G. Med Res Rev. 2021 Oct 26. doi: 10.1002/med.21862

• Fadlallah S, Julià C, García-Vallvé S, Pujadas G, Serratosa F. Drug Potency Prediction of SARS-CoV-2 Main Protease Inhibitors Based on a Graph Generative Model. Int J Mol Sci. 2023 May 15;24(10):8779. doi: 10.3390/ijms24108779.

(7) Analysis of SARS-CoV-2 mutations

• Prediction of Recurrent Mutations in SARS-CoV-2 Using Artificial Neural Networks. Saldivar-Espinoza B, Macip G, Garcia-Segura P, Mestres-Truyol J, Puigbo P, Cereto-Massague A, Pujadas G, Garcia-Vallve S. . Int. J. Mol. Sci. 2022, 23(23), 14683; https://doi.org/10.3390/ijms232314683

• Could nucleocapsid be a next-generation COVID-19 vaccine candidate? Saldivar-Espinoza B, Macip G, Pujadas G, Garcia-Vallve S. Int J Infect Dis. 2022 Nov 5;125:231-232. doi: 10.1016/j.ijid.2022.11.002.

• Saldivar-Espinoza B, Garcia-Segura P, Novau-Ferré N, Macip G, Martínez R, Puigbò P, Cereto-Massagué A, Pujadas G, Garcia-Vallve S. The Mutational Landscape of SARS-CoV-2. Int J Mol Sci. 2023 May 22;24(10):9072.

Available technology

We have a license for using the Small-Molecule Drug Discovery Suite from Schrödinger for commercial (i.e., profit) uses. Moreover, we have access to the drug discovery suites from OpenEye and Cresset (although the use of these two suites is restricted to noncommercial research). We have also an in-house database with around 225.000 natural molecules where each one is labeled with the natural sources from where they can be obtained and, therefore, we can easily make smallest databases with natural molecules obtained from particular ecosystems (e.g., marine, mediterranean, etc.).

Successful stories of our research

Our work for the cosmetic company Provital S.A. leads to the development of two cosmetic ingredients: (1) MELAVOID™ (a depigmentant which prevents spots and treats uneven skin tone); and (2) AQUAXTREM™ (that stimulates the hydration mechanisms of the skin). Both ingredients are already at the market as part of different cosmetic products. Moreover, MELAVOID™ was awarded with the 1st prize in the category "Most innovative raw material" during the BSB Innovation Prize ceremonies (In-Cosmetics Paris 2013).

Former PhD students in our group are currently working in several drug-discovery companies (e.g. Intelligent Pharma) and at the National Cancer Institute at U.S.A.