Publications

Highlights

(For a full list see below or go to Google Scholar)

Combining Virtual Reality Visualization with Ensemble Molecular Dynamics to Study Complex Protein Conformational Changes

We describe a framework that combines ensemble MD simulations and virtual reality visualization (eMD-VR) to enable users to interactively generate realistic descriptions of large amplitude, millisecond timescale protein conformational changes.

J. Juárez-Jiménez, P. Tew, M. O′Connor, S. Llabrés, R. Sage, D. Glowacki, J. Michel

J. Chem. Inf. Model. 2020, 60, 12, 6344–6354

Dynamic design: manipulation of millisecond timescale motions on the energy landscape of Cyclophilin A

Proteins need to interconvert between many conformations in order to function, many of which are formed transiently and are extremely difficult to characterize. We introduce a novel combination of accelerated MD (aMD) simulations and Markov state modelling (MSM) to explore these ‘excited’ conformational states.

J. Juárez-Jiménez, A.A. Gupta, G. Karunanithy, A.S.J.S Mey, C. Georgiou, H. Ioannidis, A. De Simone, P. N. Barlow, A.N. Hulme, M.D. Walkinshaw, A.J. Baldwin, J. Michel

Chem. Sci., 2020, 11, 2670-2680

Mechanism of the Pseudoirreversible Binding of Amantadine to the M2 Proton Channel

We nvestigated the binding of amantadine (Amt) to the wild type (wt) M2 channel and its V27A variant using multiple enhanced sampling techniques. The results allow us to propose a sequential mechanism for the (un)binding of Amt to the wt M2 channel, which involves the adoption of a transiently populated intermediate (up state) leading to the thermodynamically favored down binding mode in the channel pore. Furthermore a pseudoirreversible, kinetically driven binding mechanism is proposed as supported by modelling and experimental evidence.

S. Llabrés, J. Juárez-Jiménez, M. Masetti, R. Leiva, S. Vázquez, S. Gazzarrini, A. Moroni, A. Cavalli, F.J. Luque (*Shared first authorship)

J. Am. Chem. Soc. 2016, 138, 47, 15345–15358

Assessing the suitability of the multilevel strategy for the conformational analysis of small ligands

In this study, we assess the performance of the multilevel strategy for predicting the conformational preferences of a series of structurally related phenylethylamines and streptomycin in aqueous solution.

J. Juárez-Jiménez, X. Barril, M. Orozco, R. Pouplana, F.J. Luque

J. Phys. Chem. B 2015, 119, 3, 1164–1172

Synthesis and multi-target biological profiling of a novel family of rhein derivatives as disease-modifying anti-Alzheimer agents

We have synthesized, tested and modelled a family of rhein–huprine hybrids to hit several key targets for Alzheimer’s disease.

E. Viayna, I. Sola, M. Bartolini, A. De Simone, C. Tapia-Rojas, F.G. Serrano, R. Sabaté Lagunas, J. Juárez-Jiménez, B. Pérez Fernández, F.J. Luque, V. Andrisano, M. Clos, N.C. Inestrosa, D. Muñoz-Torrero

J. Med. Chem. 2014, 57, 6, 2549–2567

Synthesis, Biological Evaluation, and Molecular Modeling of Donepezil and N-[(5-(Benzyloxy)-1-methyl-1H-indol-2-yl)methyl]-N-methylprop-2-yn-1-amine Hybrids as New Multipotent Cholinesterase/Monoamine Oxidase Inhibitors for the Treatment of Alzheimer’s Disease

A new family of multitarget molecules able to interact with acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), as well as with monoamino oxidase (MAO) A and B was synthesized, tested and modelled. The results suggest that the new compounds are promising multitarget drug candidates with potential impact for Alzheimer’s disease therapy.

I. Bolea, J. Juárez-Jiménez, C. de los Rı́os, M. Chioua, R. Pouplana, F.J. Luque, M. Unzeta, J. Marco-Contelles, A. Samadi (*Shared first authorship)

J. Med. Chem. 2011, 54, 24, 8251–8270

 

Preprints

  1. Lenalidomide stabilizes protein-protein complexes by turning labile intermolecular H-bonds into robust interactions

Full List

  1. A fluorogenic probe for granzyme B enables in-biopsy evaluation and screening of response to anticancer immunotherapies.
    2. J. Scott, L. Mendive-Tapia, D. Gordon, N. D. Barth, E. J. Thompson, Z. Cheng, D. Taggart, T. Kitamura, A. Bravo-Blas, E. W. Roberts, J. Juárez-Jiménez, J. Michel, B. Piet, I. Jolanda de Vries, M. Verdoes, J. Dawson, N. O. Carragher, R. A. O'Connor, A. R. Akram, M. Frame, A. Serrels, M. Vendrell
    Nat. Commun. 2022, 13, 2366
  2. Discovery and In Vivo Proof of Concept of a Highly Potent Dual Inhibitor of Soluble Epoxide Hydrolase and Acetylcholinesterase for the Treatment of Alzheimer’s Disease
    3. S. Codony, C. Pont, C. Griñán-Ferré, A. Di Pede-Mattatelli, C. Calvó-Tusell, F. Feixas, S. Osuna, J. Jarné-Ferrer, M. Naldi, M. Bartolini, M.I. Loza, J. Brea, B. Pérez, C. Bartra, C. Sanfeliu, J. Juárez-Jiménez, C. Morisseau, B.D. Hammock, M. Pallàs, S. Vázquez, D. Muñoz-Torrero
    J. Med. Chem. 2022, 65, 6, 4909–4925
  3. Dual Effect of Prussian Blue Nanoparticles on Aβ40 Aggregation: β-Sheet Fibril Reduction and Copper Dyshomeostasis Regulation
    4. J. Kowalczyk, E. Grapsi, A. Espargaró, A.B. Caballero, J. Juárez-Jiménez, M.A. Busquets, P. Gamez, R. Sabate, J. Estelrich.
    Biomacromolecules 2021, 22, 2, 430–440
  4. Combining Virtual Reality Visualization with Ensemble Molecular Dynamics to Study Complex Protein Conformational Changes
    5. J. Juárez-Jiménez, P. Tew, M. O′Connor, S. Llabrés, R. Sage, D. Glowacki, J. Michel
    J. Chem. Inf. Model. 2020, 60, 12, 6344–6354
  5. Investigating Cryptic Binding Sites by Molecular Dynamics Simulations
    6. A. Kuzmanic, G.R. Bowman, J. Juárez-Jiménez, J. Michel, F.L. Gervasio
    Acc. Chem. Res. 2020, 53, 3, 654–661
  6. Dynamic design: manipulation of millisecond timescale motions on the energy landscape of Cyclophilin A
    7. J. Juárez-Jiménez, A.A. Gupta, G. Karunanithy, A.S.J.S Mey, C. Georgiou, H. Ioannidis, A. De Simone, P. N. Barlow, A.N. Hulme, M.D. Walkinshaw, A.J. Baldwin, J. Michel
    Chem. Sci., 2020, 11, 2670-2680
  7. A computationally designed binding mode flip leads to a novel class of potent tri-vector cyclophilin inhibitors
    8. A. De Simone, C. Georgiou, H. Ioannidis, A.A. Gupta, J. Juárez-Jiménez, D. Doughty-Shenton, E.A. Blackburn, M.A. Wear, J.P. Richards, P.N. Barlow, N. Carragher, M.D. Walkinshaw, A.N. Hulme, J. Michel
    Chem. Sci., 2019, 10, 542-547
  8. First homology model of Plasmodium falciparum glucose-6-phosphate dehydrogenase: Discovery of selective substrate analog-based inhibitors as novel antimalarial agents
    9. N. Alencar, I. Sola, M. Linares, J. Juárez-Jiménez, C. Pont, A. Viayna, D. Vilchez, C. Sampedro, P. Abad, S. Perez-Benavente, J. Lameira, J.M. Bautista, D. Muñoz-Torrero, F.J. Luque
    Eur. J. Med. Chem. 146, 2018, 108-122
  9. Impact of domain knowledge on blinded predictions of binding energies by alchemical free energy calculations
    10. A.S.J.S. Mey, J. Juárez-Jiménez, J. Michel
    J. Comput. Aided Mol. Des. 32, 2018, 199–210
  10. Tetrahydrobenzothiophene carboxamides: Beyond the kinase domain and into the fatty acid realm
    11. S. Llona-Minguez, S. Fayezi, A. Alihemmati, J. Juárez-Jiménez, F.J. Piedrafita, T. Helleday
    Bioorganic Med. Chem. Lett. 27 (18), 2017, 4462–4466 (2018)
  11. Unveiling a novel transient druggable pocket in BACE-1 through molecular simulations: Conformational analysis and binding mode of multisite inhibitors
    12. O. Di Pietro, J. Juarez-Jimenez, D. Munoz-Torrero, C.A. Laughton, F.J. Luque
    PloS one 12 (5), e0177683
  12. Tuning the local solvent composition at a drug carrier surface: the effect of dimethyl sulfoxide/water mixture on the photofunctional properties of hypericin–β-lactoglobulin complexes
    13. P. Delcanale, B. Rodríguez-Amigo, J. Juárez-Jiménez, F.J. Luque, S. Abbruzzetti, M. Agut, S. Nonell, C. Viappiani
    J. Mater. Chem. B, 2017, 5, 1633-1641
  13. Mechanism of the Pseudoirreversible Binding of Amantadine to the M2 Proton Channel
    14. S. Llabrés*, J. Juárez-Jiménez*, M. Masetti, R. Leiva, S. Vázquez, S. Gazzarrini, A. Moroni, A. Cavalli, F.J. Luque (*Shared first authorship)
    J. Am. Chem. Soc. 2016, 138, 47, 15345–15358
  14. Blinded predictions of binding modes and energies of HSP90-α ligands for the 2015 D3R grand challenge
    15. A.S.J.S. Mey*, J. Juárez-Jiménez*, A. Hennessy, J. Michel (*Shared first authorship)
    Bioorganic Med. Chem. 24 (20) 2016, 4890-4899
  15. Design, synthesis and biological evaluation of N-methyl-N-[(1, 2, 3-triazol-4-yl) alkyl] propargylamines as novel monoamine oxidase B inhibitors
    16. O. Di Pietro, N. Alencar, G. Esteban, E. Viayna, N. Szałaj, J. Vázquez, J. Juárez-Jiménez, I.Sola, B. Pérez, M. Solé, M. Unzeta, D. Muñoz-Torrero, F.J. Luque
    Bioorganic Med. Chem. 24 (20) 2016, 4835-4854
  16. New polycyclic dual inhibitors of the wild type and the V27A mutant M2 channel of the influenza A virus with unexpected binding mode
    17. M. Rey-Carrizo, S. Gazzarrini, S. Llabrés, M. Frigolé-Vivas, J. Juárez-Jiménez, M. Font-Bardia, L. Naesens, A. Moroni, F.J. Luque, S. Vázquez
    Eur. J. Med. Chem. 146, 2015, 318-329
  17. The complex of hypericin with β-lactoglobulin has antimicrobial activity with potential applications in dairy industry
    18. B. Rodríguez-Amigo, P. Delcanale, G. Rotger, J. Juárez-Jiménez, S. Abbruzzetti, A. Summer, M. Agut, F.J. Luque, S. Nonell, C. Viappiani
    J. Dairy Sci. 98 (1), 2015, 89-94
  18. Assessing the suitability of the multilevel strategy for the conformational analysis of small ligands
    19. J. Juárez-Jiménez, X. Barril, M. Orozco, R. Pouplana, F.J. Luque
    J. Phys. Chem. B 2015, 119, 3, 1164–1172
  19. Tetrahydrobenzo [h][1, 6] naphthyridine-6-chlorotacrine hybrids as a new family of anti-Alzheimer agents targeting β-amyloid, tau, and cholinesterase pathologies
    20. O. Di Pietro, F.J. Pérez-Areales, J. Juárez-Jiménez, A. Espargaró, M.V. Clos, B. Pérez, R. Lavilla, R. Sabaté, F.J. Luque, D. Muñoz-Torrero
    Eur. J. Med. Chem. 84, 2014, 107-117
  20. Easily accessible polycyclic amines that inhibit the wild-type and amantadine-resistant mutants of the M2 channel of influenza A virus
    21. M. Rey-Carrizo, M. Barniol-Xicota, C. Ma, M. Frigolé-Vivas, E. Torres, L. Naesens, S. Llabrés, J. Juárez-Jiménez, F.J. Luque, W.F. DeGrado, R.A. Lamb, L.H. Pinto, S. Vázquez
    J. Med. Chem. 2014, 57, 13, 5738–5747
  21. Synthesis and multi-target biological profiling of a novel family of rhein derivatives as disease-modifying anti-Alzheimer agents
    22. E. Viayna, I. Sola, M. Bartolini, A. De Simone, C. Tapia-Rojas, F.G. Serrano, R. Sabaté Lagunas, J. Juárez-Jiménez, B. Pérez Fernández, F.J. Luque, V. Andrisano, M. Clos, N.C. Inestrosa, D. Muñoz-Torrero
    J. Med. Chem. 2014, 57, 6, 2549–2567
  22. Exploring the structural basis of the selective inhibition of monoamine oxidase A by dicarbonitrile aminoheterocycles: Role of Asn181 and Ile335 validated by spectroscopic and computational studies
    23. J. Juárez-Jiménez, E. Mendes, C. Galdeano, C. Martins, D.B. Silva, J. Marco-Contelles, M.C. Carreiras, F.J. Luque, R.R. Ramsay
    Biochim. Biophys. Acta Proteins Proteom 1844, 2, 2014 389–397
  23. 1,2,3,4-Tetrahydrobenzo[h][1,6]naphthyridines as a new family of potent peripheral-to-midgorge-site inhibitors of acetylcholinesterase: Synthesis, pharmacological evaluation and mechanistic studies
    24. O. Di Pietro, E. Viayna, E. Vicente-García, M. Bartolini, R. Ramón, J. Juárez-Jiménez, M.V. Clos, B. Pérez, V. Andrisano, F.J. Luque, R. Lavilla, D. Muñoz-Torrero
    Eur. J. Med. Chem. 73, 2014, 141-152
  24. Synthesis, Biological Evaluation, and Molecular Modeling of Donepezil and N-[(5-(Benzyloxy)-1-methyl-1H-indol-2-yl)methyl]-N-methylprop-2-yn-1-amine Hybrids as New Multipotent Cholinesterase/Monoamine Oxidase Inhibitors for the Treatment of Alzheimer’s Disease
    25. I. Bolea*, J. Juárez-Jiménez*, C. de los Rı́os, M. Chioua, R. Pouplana, F.J. Luque, M. Unzeta, J. Marco-Contelles, A. Samadi (*Shared first authorship)
    J. Med. Chem. 2011, 54, 24, 8251–8270
  25. Exploring the size limit of templates for inhibitors of the M2 ion channel of influenza A virus
    26. M.D. Duque, C. Ma, E. Torres, J. Wang, L. Naesens, J. Juárez-Jiménez, P. Camps, F.J. Luque, W.F. DeGrado, R.A. Lamb, L.H. Pinto, S. Vázquez
    J. Med. Chem. 2011, 54, 8, 2646–2657