The Structural Bioinformatics Group focuses on developing innovative techniques for modeling, analyzing, and simulating molecular structures, in close collaboration with experimental labs. We are particularly interested in large macromolecules with dynamic composition and conformation, whose actions and interactions are essential for cellular function. Our research includes integrating structural information at different resolutions, protein stability, protein design, molecular flexibility, loop modeling, and the prediction of protein-protein and protein-ligand interactions. The developed methodologies are available through software distributions and web servers
Biomolecular simulation, Computational models and simulations, Deep Learning in Biology, Experimental structure determination, Molecular flexibility, Molecular Interactions/Docking, Mutation Analysis and design, Protein/Nucleic Acid design, Structural bioinformatics, Structure prediction, Structure-function relationship
Publications
Pepe, A., Lasenby, J., & Chacon, P. (2024). Geometric Algebra Models of Proteins for Three-Dimensional Structure Prediction: A Detailed Analysis. Advanced Computational Applications of Geometric Algebra, 141–159. https://doi.org/10.1007/978-3-031-55985-3_6
Alcorlo, M., Luque-Ortega, J. R., Gago, F., Ortega, A., Castellanos, M., Chacón, P., de Vega, M., Blanco, L., Hermoso, J. M., Serrano, M., Rivas, G., & Hermoso, J. A. (2024). Flexible structural arrangement and DNA-binding properties of protein p6 from Bacillus subtillis phage φ29. Nucleic Acids Research, 52(4), 2045–2065. https://doi.org/10.1093/nar/gkae041
Pepe, A., Lasenby, J., & Chacón, P. (2023). Using a Graph Transformer Network to Predict 3D Coordinates of Proteins via Geometric Algebra Modelling. Empowering Novel Geometric Algebra for Graphics and Engineering, 83–95. https://doi.org/10.1007/978-3-031-30923-6_7
Hernández, I. M., Dehouck, Y., Bastolla, U., López-Blanco, J. R., & Chacón, P. (2023). Predicting protein stability changes upon mutation using a simple orientational potential. Bioinformatics, 39(1). https://doi.org/10.1093/bioinformatics/btad011
Gao, Z., Tan, C., Chacón, P., & Li, S. Z. (2022). <i>PiFold: Toward effective and efficient protein inverse folding</i> (Version 4). arXiv. https://doi.org/10.48550/ARXIV.2209.12643
Bueno-Carrasco, M. T., Cuéllar, J., Flydal, M. I., Santiago, C., Kråkenes, T.-A., Kleppe, R., López-Blanco, J. R., Marcilla, M., Teigen, K., Alvira, S., Chacón, P., Martinez, A., & Valpuesta, J. M. (2022). Structural mechanism for tyrosine hydroxylase inhibition by dopamine and reactivation by Ser40 phosphorylation. Nature Communications, 13(1). https://doi.org/10.1038/s41467-021-27657-y
Pepe, A., Lasenby, J., & Chacón, P. (2022). Learning rotations. Mathematical Methods in the Applied Sciences, 47(3), 1204–1217. Portico. https://doi.org/10.1002/mma.8698
López-Blanco, J. R., Dehouck, Y., Bastolla, U., & Chacón, P. (2022). Local Normal Mode Analysis for Fast Loop Conformational Sampling. Journal of Chemical Information and Modeling, 62(18), 4561–4568. https://doi.org/10.1021/acs.jcim.2c00870
Barozet, A., Chacón, P., & Cortés, J. (2021). Current approaches to flexible loop modeling. Current Research in Structural Biology, 3, 187–191. https://doi.org/10.1016/j.crstbi.2021.07.002
Quignot, C., Postic, G., Bret, H., Rey, J., Granger, P., Murail, S., Chacón, P., Andreani, J., Tufféry, P., & Guerois, R. (2021). InterEvDock3: a combined template-based and free docking server with increased performance through explicit modeling of complex homologs and integration of covariation-based contact maps. Nucleic Acids Research, 49(W1), W277–W284. https://doi.org/10.1093/nar/gkab358
Valpuesta, J., Bueno-Carrasco, T., Cuellar, J., Flydal, M., Santiago, C., Kråkenes, T.-A., Kleppe, R., López-Blanco, J., Teigen, K., Alvira, S., Chacon, P., & Martínez, A. (2020). The Structure of Human Tyrosine Hydroxylase Reveals the Mechanism for Feedback Inhibition by Dopamine. https://doi.org/10.21203/rs.3.rs-64971/v1
Melero, R., Sorzano, C. O. S., Foster, B., Vilas, J.-L., Martínez, M., Marabini, R., Ramírez-Aportela, E., Sanchez-Garcia, R., Herreros, D., del Caño, L., Losana, P., Fonseca-Reyna, Y. C., Conesa, P., Wrapp, D., Chacon, P., McLellan, J. S., Tagare, H. D., & Carazo, J.-M. (2020). Continuous flexibility analysis of SARS-CoV-2 Spike prefusion structures. https://doi.org/10.1101/2020.07.08.191072
Quignot, C., Granger, P., Chacón, P., Guerois, R., & Andreani, J. (2020). Atomic-level evolutionary information improves protein-protein interface scoring. https://doi.org/10.1101/2020.10.26.355073
Kadukova, M., Machado, K. dos S., Chacón, P., & Grudinin, S. (2020). KORP-PL: a coarse-grained knowledge-based scoring function for protein–ligand interactions. Bioinformatics, 37(7), 943–950. https://doi.org/10.1093/bioinformatics/btaa748
López-Blanco, J. R., & Chacón, P. (2019). KORP: knowledge-based 6D potential for fast protein and loop modeling. Bioinformatics, 35(17), 3013–3019. https://doi.org/10.1093/bioinformatics/btz026
Artola, M., Ruíz-Avila, L. B., Ramírez-Aportela, E., Martínez, R. F., Araujo-Bazán, L., Vázquez-Villa, H., Martín-Fontecha, M., Oliva, M. A., Martín-Galiano, A. J., Chacón, P., López-Rodríguez, M. L., Andreu, J. M., & Huecas, S. (2017). The structural assembly switch of cell division protein FtsZ probed with fluorescent allosteric inhibitors. Chemical Science, 8(2), 1525–1534. https://doi.org/10.1039/c6sc03792e
Tenthorey, J. L., Haloupek, N., López-Blanco, J. R., Grob, P., Adamson, E., Hartenian, E., Lind, N. A., Bourgeois, N. M., Chacón, P., Nogales, E., & Vance, R. E. (2017). The structural basis of flagellin detection by NAIP5: A strategy to limit pathogen immune evasion. Science, 358(6365), 888–893. https://doi.org/10.1126/science.aao1140
Louder, R. K., He, Y., López-Blanco, J. R., Fang, J., Chacón, P., & Nogales, E. (2016). Structure of promoter-bound TFIID and model of human pre-initiation complex assembly. Nature, 531(7596), 604–609. https://doi.org/10.1038/nature17394
López-Blanco, J. R., Canosa-Valls, A. J., Li, Y., & Chacón, P. (2016). RCD+: Fast loop modeling server. Nucleic Acids Research, 44(W1), W395–W400. https://doi.org/10.1093/nar/gkw395
López-Blanco, J. R., & Chacón, P. (2016). New generation of elastic network models. Current Opinion in Structural Biology, 37, 46–53. https://doi.org/10.1016/j.sbi.2015.11.013
Kellogg, E. H., Howes, S., Ti, S.-C., Ramírez-Aportela, E., Kapoor, T. M., Chacón, P., & Nogales, E. (2016). Near-atomic cryo-EM structure of PRC1 bound to the microtubule. Proceedings of the National Academy of Sciences, 113(34), 9430–9439. https://doi.org/10.1073/pnas.1609903113
Ramírez-Aportela, E., López-Blanco, J. R., & Chacón, P. (2016). FRODOCK 2.0: fast protein–protein docking server. Bioinformatics, 32(15), 2386–2388. https://doi.org/10.1093/bioinformatics/btw141
Aliaga, J. I., Alonso, P., Badía, J. M., Chacón, P., Davidović, D., López-Blanco, J. R., & Quintana-Ortí, E. S. (2016). A fast band–Krylov eigensolver for macromolecular functional motion simulation on multicore architectures and graphics processors. Journal of Computational Physics, 309, 314–323. https://doi.org/10.1016/j.jcp.2016.01.007
Ramírez-Aportela, E., López-Blanco, J. R., Andreu, J. M., & Chacon, P. (2015). Molecular Dynamics and Assembly Switch of FtsZ Filaments. Biophysical Journal, 108(2), 527a. https://doi.org/10.1016/j.bpj.2014.11.2889
Canosa-Valls, A. J., Ramírez-Aportela, E., Chacón, P., & López-Blanco, J. R. (2015). Integrative Modeling Approaches to Interpret High-Resolution cryo-EM Reconstructions. Biophysical Journal, 108(2), 472a. https://doi.org/10.1016/j.bpj.2014.11.2582
Ramírez-Aportela, E., López-Blanco, J. R., Andreu, J. M., & Chacón, P. (2014). Understanding Nucleotide-Regulated FtsZ Filament Dynamics and the Monomer Assembly Switch with Large-Scale Atomistic Simulations. Biophysical Journal, 107(9), 2164–2176. https://doi.org/10.1016/j.bpj.2014.09.033
Silva-Martín, N., Bartual, S. G., Ramírez-Aportela, E., Chacón, P., Park, C. G., & Hermoso, J. A. (2014). Structural Basis for Selective Recognition of Endogenous and Microbial Polysaccharides by Macrophage Receptor SIGN-R1. Structure, 22(11), 1595–1606. https://doi.org/10.1016/j.str.2014.09.001
López‐Blanco, J. R., Miyashita, O., Tama, F., & Chacón, P. (2014). Normal Mode Analysis Techniques in Structural Biology. Encyclopedia of Life Sciences. Portico. https://doi.org/10.1002/9780470015902.a0020204.pub2
López-Blanco, J. R., Ramirez, E., Garcia, S., & Chacon, P. (2014). Imods: Fast Exploration of Macromolecular Collective Motions. Biophysical Journal, 106(2), 653a. https://doi.org/10.1016/j.bpj.2013.11.3614
López-Blanco, J. R., Aliaga, J. I., Quintana-Ortí, E. S., & Chacón, P. (2014). iMODS: internal coordinates normal mode analysis server. Nucleic Acids Research, 42(W1), W271–W276. https://doi.org/10.1093/nar/gku339
Sanchez, S. G., Aportela, E. R., Garzon, J. I., Chacon, P., Montemayor, A. S., & Cabido, R. (2014). FRODRUG: A Virtual Screening GPU Accelerated Approach for Drug Discovery. 2014 22nd Euromicro International Conference on Parallel, Distributed, and Network-Based Processing, 594–600. https://doi.org/10.1109/pdp.2014.64
Krüger, D. M., Ignacio Garzón, J., Chacón, P., & Gohlke, H. (2014). DrugScorePPI Knowledge-Based Potentials Used as Scoring and Objective Function in Protein-Protein Docking. PLoS ONE, 9(2), e89466. https://doi.org/10.1371/journal.pone.0089466
López‐Blanco, J. R., & Chacón, P. (2014). Structural modeling from electron microscopy data. WIREs Computational Molecular Science, 5(1), 62–81. Portico. https://doi.org/10.1002/wcms.1199
Artola, M., Ruiz-Avila, L. B., Vergoñós, A., Huecas, S., Araujo-Bazán, L., Martín-Fontecha, M., Vázquez-Villa, H., Turrado, C., Ramírez-Aportela, E., Hoegl, A., Nodwell, M., Barasoain, I., Chacón, P., Sieber, S. A., Andreu, J. M., & López-Rodríguez, M. L. (2014). Effective GTP-Replacing FtsZ Inhibitors and Antibacterial Mechanism of Action. ACS Chemical Biology, 10(3), 834–843. https://doi.org/10.1021/cb500974d
Ruiz-Avila, L. B., Huecas, S., Artola, M., Vergoñós, A., Ramírez-Aportela, E., Cercenado, E., Barasoain, I., Vázquez-Villa, H., Martín-Fontecha, M., Chacón, P., López-Rodrı́guez, M. L., & Andreu, J. M. (2013). Synthetic Inhibitors of Bacterial Cell Division Targeting the GTP-Binding Site of FtsZ. ACS Chemical Biology, 8(9), 2072–2083. https://doi.org/10.1021/cb400208z
Chys, P., & Chacón, P. (2013). Random Coordinate Descent with Spinor-matrices and Geometric Filters for Efficient Loop Closure. Journal of Chemical Theory and Computation, 9(3), 1821–1829. https://doi.org/10.1021/ct300977f
Lopéz-Blanco, J. R., & Chacón, P. (2013). iMODFIT: Efficient and robust flexible fitting based on vibrational analysis in internal coordinates. Journal of Structural Biology, 184(2), 261–270. https://doi.org/10.1016/j.jsb.2013.08.010
Estrin, E., Lopez-Blanco, J. R., Chacón, P., & Martin, A. (2013). Formation of an Intricate Helical Bundle Dictates the Assembly of the 26S Proteasome Lid. Structure, 21(9), 1624–1635. https://doi.org/10.1016/j.str.2013.06.023
López-Blanco, J. R., Reyes, R., Aliaga, J. I., Badia, R. M., Chacón, P., & Quintana-Ortí, E. S. (2013). Exploring large macromolecular functional motions on clusters of multicore processors. Journal of Computational Physics, 246, 275–288. https://doi.org/10.1016/j.jcp.2013.03.032
Lopez-Blanco, J. R., Ramirez, E., Garcia, S., & Chacon, P. (2013). Exploring Macromolecular Machine Motions. Biophysical Journal, 104(2), 69a. https://doi.org/10.1016/j.bpj.2012.11.418
Chys, P., & Chacón, P. (2012). Spinor product computations for protein conformations. Journal of Computational Chemistry, 33(21), 1717–1729. Portico. https://doi.org/10.1002/jcc.23002
Pesonen, J., Henriksson, K. O. E., López-Blanco, J. R., & Chacón, P. (2012). Normal mode analysis of molecular motions in curvilinear coordinates on a non-Eckart body-frame: an application to protein torsion dynamics. Journal of Mathematical Chemistry, 50(6), 1521–1549. https://doi.org/10.1007/s10910-012-9987-8
Ramon Lopez-Blanco, J., Ramirez-Aportela, E., Garcia-Sanchez, S., Chys, P., & Chacon, P. (2012). Modeling Macromolecular Flexibility with Normal Mode Analysis in Internal Coordinates. Biophysical Journal, 102(3), 394a. https://doi.org/10.1016/j.bpj.2011.11.2155
HENRIKSSON, K. O. E., PESONEN, J., & CHACON, P. (2012). CURVILINEAR DYNAMICS OF PROTEIN COMPLEXES. Journal of Theoretical and Computational Chemistry, 11(03), 675–696. https://doi.org/10.1142/s0219633612500459
Lopéz-Blanco, J. R., Garzón, J. I., & Chacón, P. (2011). iMod: multipurpose normal mode analysis in internal coordinates. Bioinformatics, 27(20), 2843–2850. https://doi.org/10.1093/bioinformatics/btr497
Schaffner-Barbero, C., Martín-Fontecha, M., Chacón, P., & Andreu, J. M. (2011). Targeting the Assembly of Bacterial Cell Division Protein FtsZ with Small Molecules. ACS Chemical Biology, 7(2), 269–277. https://doi.org/10.1021/cb2003626
Orellana, L., Rueda, M., Ferrer-Costa, C., Lopez-Blanco, J. R., Chacón, P., & Orozco, M. (2010). Approaching Elastic Network Models to Molecular Dynamics Flexibility. Journal of Chemical Theory and Computation, 6(9), 2910–2923. https://doi.org/10.1021/ct100208e
Buey, R. M., Chacón, P., Andreu, J. M., & Díaz, J. F. (2009). Protein Shape and Assembly Studied with X-Ray Solution Scattering: Fundaments and Practice. Applications of Synchrotron Light to Scattering and Diffraction in Materials and Life Sciences, 245–263. https://doi.org/10.1007/978-3-540-95968-7_12
Boer, D. R., Ruíz-Masó, J. A., López-Blanco, J. R., Blanco, A. G., Vives-Llàcer, M., Chacón, P., Usón, I., Gomis-Rüth, F. X., Espinosa, M., Llorca, O., del Solar, G., & Coll, M. (2009). Plasmid replication initiator RepB forms a hexamer reminiscent of ring helicases and has mobile nuclease domains. The EMBO Journal, 28(11), 1666–1678. https://doi.org/10.1038/emboj.2009.125
Garzon, J. I., Lopéz-Blanco, J. R., Pons, C., Kovacs, J., Abagyan, R., Fernandez-Recio, J., & Chacon, P. (2009). FRODOCK: a new approach for fast rotational protein–protein docking. Bioinformatics, 25(19), 2544–2551. https://doi.org/10.1093/bioinformatics/btp447
Abia, D., Bastolla, U., Chacón, P., Fábrega, C., Gago, F., Morreale, A., & Tramontano, A. (2009). In memoriam. Proteins: Structure, Function, and Bioinformatics, 78(1). Portico. https://doi.org/10.1002/prot.22660
Ignacio Garzon, J., Huedo, E., Santiago Montero, R., Martin Llorente, I., & Chacon, P. (2009). End-To-End Cache System for Grid Computing: Design and Efficiency Analysis of a High-Throughput Bioinformatic Docking Application. The International Journal of High Performance Computing Applications, 24(3), 243–264. https://doi.org/10.1177/1094342009350469
Torreira, E., Jha, S., López-Blanco, J. R., Arias-Palomo, E., Chacón, P., Cañas, C., Ayora, S., Dutta, A., & Llorca, O. (2008). Architecture of the Pontin/Reptin Complex, Essential in the Assembly of Several Macromolecular Complexes. Structure, 16(10), 1511–1520. https://doi.org/10.1016/j.str.2008.08.009
Rueda, M., Chacón, P., & Orozco, M. (2007). Thorough Validation of Protein Normal Mode Analysis: A Comparative Study with Essential Dynamics. Structure, 15(5), 565–575. https://doi.org/10.1016/j.str.2007.03.013
Buey, R. M., Monterroso, B., Menéndez, M., Diakun, G., Chacón, P., Hermoso, J. A., & Díaz, J. F. (2007). Insights into Molecular Plasticity of Choline Binding Proteins (Pneumococcal Surface Proteins) by SAXS. Journal of Molecular Biology, 365(2), 411–424. https://doi.org/10.1016/j.jmb.2006.09.091
Garzon, J. I., Huedo, E., Montero, R. S., Llorente, I. M., & Chacon, P. (2007). Grid Multi-Resolution Docking. 15th EUROMICRO International Conference on Parallel, Distributed and Network-Based Processing (PDP’07), 3–10. https://doi.org/10.1109/pdp.2007.48
Martín-Benito, J., Gómez-Reino, J., Stirling, P. C., Lundin, V. F., Gómez-Puertas, P., Boskovic, J., Chacón, P., Fernández, J. J., Berenguer, J., Leroux, M. R., & Valpuesta, J. M. (2007). Divergent Substrate-Binding Mechanisms Reveal an Evolutionary Specialization of Eukaryotic Prefoldin Compared to Its Archaeal Counterpart. Structure, 15(1), 101–110. https://doi.org/10.1016/j.str.2006.11.006
Garzón, J. I., Kovacs, J., Abagyan, R., & Chacón, P. (2007). DFprot: a webtool for predicting local chain deformability. Bioinformatics, 23(7), 901–902. https://doi.org/10.1093/bioinformatics/btm014
Garzón, J. I., Kovacs, J., Abagyan, R., & Chacón, P. (2006). ADP_EM: fast exhaustive multi-resolution docking for high-throughput coverage. Bioinformatics, 23(4), 427–433. https://doi.org/10.1093/bioinformatics/btl625
Wriggers, W., Chacón, P., A. Kovacs, J., Tama, F., & Birmanns, S. (2004). Topology representing neural networks reconcile biomolecular shape, structure, and dynamics. Neurocomputing, 56, 365–379. https://doi.org/10.1016/j.neucom.2003.09.007
Kovacs, J. A., Chacón, P., & Abagyan, R. (2004). Predictions of protein flexibility: First‐order measures. Proteins: Structure, Function, and Bioinformatics, 56(4), 661–668. Portico. https://doi.org/10.1002/prot.20151
Boskovic, J. (2003). Visualization of DNA-induced conformational changes in the DNA repair kinase DNA-PKcs. The EMBO Journal, 22(21), 5875–5882. https://doi.org/10.1093/emboj/cdg555
Opalka, N., Chlenov, M., Chacon, P., Rice, W. J., Wriggers, W., & Darst, S. A. (2003). Structure and Function of the Transcription Elongation Factor GreB Bound to Bacterial RNA Polymerase. Cell, 114(3), 335–345. https://doi.org/10.1016/s0092-8674(03)00600-7
Chacón, P., Tama, F., & Wriggers, W. (2003). Mega-Dalton Biomolecular Motion Captured from Electron Microscopy Reconstructions. Journal of Molecular Biology, 326(2), 485–492. https://doi.org/10.1016/s0022-2836(02)01426-2
Kovacs, J. A., Chacón, P., Cong, Y., Metwally, E., & Wriggers, W. (2003). Fast rotational matching of rigid bodies by fast Fourier transform acceleration of five degrees of freedom. Acta Crystallographica Section D Biological Crystallography, 59(8), 1371–1376. https://doi.org/10.1107/s0907444903011247
Chacón, P., & Wriggers, W. (2002). Multi-resolution contour-based fitting of macromolecular structures. Journal of Molecular Biology, 317(3), 375–384. https://doi.org/10.1006/jmbi.2002.5438
Darst, S. A., Opalka, N., Chacon, P., Polyakov, A., Richter, C., Zhang, G., & Wriggers, W. (2002). Conformational flexibility of bacterial RNA polymerase. Proceedings of the National Academy of Sciences, 99(7), 4296–4301. https://doi.org/10.1073/pnas.052054099
Wriggers, W., & Chacón, P. (2001). UsingSitusfor the registration of protein structures with low-resolution bead models from X-ray solution scattering. Journal of Applied Crystallography, 34(6), 773–776. https://doi.org/10.1107/s0021889801012869
Wriggers, W., & Chacón, P. (2001). Modeling Tricks and Fitting Techniques for Multiresolution Structures. Structure, 9(9), 779–788. https://doi.org/10.1016/s0969-2126(01)00648-7
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