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612 results on '"Tuñón, Iñaki"'

1. The need to implement FAIR principles in biomolecular simulations

Author

Amaro, Rommie, Åqvist, Johan, Bahar, Ivet, Battistini, Federica, Bellaiche, Adam, Beltran, Daniel, Biggin, Philip C., Bonomi, Massimiliano, Bowman, Gregory R., Bryce, Richard, Bussi, Giovanni, Carloni, Paolo, Case, David, Cavalli, Andrea, Chang, Chie-En A., Cheatham III, Thomas E., Cheung, Margaret S., Chipot, Cris, Chong, Lillian T., Choudhary, Preeti, Cisneros, Gerardo Andres, Clementi, Cecilia, Collepardo-Guevara, Rosana, Coveney, Peter, Covino, Roberto, Crawford, T. Daniel, Peraro, Matteo Dal, de Groot, Bert, Delemotte, Lucie, De Vivo, Marco, Essex, Jonathan, Fraternali, Franca, Gao, Jiali, Gelpí, Josep Lluís, Gervasio, Francesco Luigi, Gonzalez-Nilo, Fernando Danilo, Grubmüller, Helmut, Guenza, Marina, Guzman, Horacio V., Harris, Sarah, Head-Gordon, Teresa, Hernandez, Rigoberto, Hospital, Adam, Huang, Niu, Huang, Xuhui, Hummer, Gerhard, Iglesias-Fernández, Javier, Jensen, Jan H., Jha, Shantenu, Jiao, Wanting, Jorgensen, William L., Kamerlin, Shina Caroline Lynn, Khalid, Syma, Laughton, Charles, Levitt, Michael, Limongelli, Vittorio, Lindahl, Erik, Lindorff-Larsen, Kresten, Loverde, Sharon, Lundborg, Magnus, Luo, Yun Lyna, Luque, Francisco Javier, Lynch, Charlotte I., MacKerell, Alexander, Magistrato, Alessandra, Marrink, Siewert J., Martin, Hugh, McCammon, J. Andrew, Merz, Kenneth, Moliner, Vicent, Mulholland, Adrian, Murad, Sohail, Naganathan, Athi N., Nangia, Shikha, Noe, Frank, Noy, Agnes, Oláh, Julianna, O'Mara, Megan, Ondrechen, Mary Jo, Onuchic, José N., Onufriev, Alexey, Osuna, Silvia, Panchenko, Anna R., Pantano, Sergio, Parish, Carol, Parrinello, Michele, Perez, Alberto, Perez-Acle, Tomas, Perilla, Juan R., Pettitt, B. Montgomery, Pietropalo, Adriana, Piquemal, Jean-Philip, Poma, Adolfo, Praprotnik, Matej, Ramos, Maria J., Ren, Pengyu, Reuter, Nathalie, Roitberg, Adrian, Rosta, Edina, Rovira, Carme, Roux, Benoit, Röthlisberger, Ursula, Sanbonmatsu, Karissa Y., Schlick, Tamar, Shaytan, Alexey K., Simmerling, Carlos, Smith, Jeremy C., Sugita, Yuji, Świderek, Katarzyna, Taiji, Makoto, Tao, Peng, Tikhonova, Irina G., Tirado-Rives, Julian, Tunón, Inaki, Van Der Kamp, Marc W., Van der Spoel, David, Velankar, Sameer, Voth, Gregory A., Wade, Rebecca, Warshel, Ariel, Welborn, Valerie Vaissier, Wetmore, Stacey, Wong, Chung F., Yang, Lee-Wei, Zacharias, Martin, and Orozco, Modesto

Subjects
Quantitative Biology - Biomolecules
Abstract

This letter illustrates the opinion of the molecular dynamics (MD) community on the need to adopt a new FAIR paradigm for the use of molecular simulations. It highlights the necessity of a collaborative effort to create, establish, and sustain a database that allows findability, accessibility, interoperability, and reusability of molecular dynamics simulation data. Such a development would democratize the field and significantly improve the impact of MD simulations on life science research. This will transform our working paradigm, pushing the field to a new frontier. We invite you to support our initiative at the MDDB community (https://mddbr.eu/community/)

Published
2024

3. Sub-picosecond molecular dynamics modulate the energies of spin states for hundreds of nanoseconds

Author

Rosaleny, Lorena E., Zinovjev, Kirill, Tuñón, Iñaki, and Gaita-Ariño, Alejandro

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

Molecular vibrations are increasingly seen as a key factor for spin dynamics in single-ion magnets and molecular spin qubits. Herein we show how an inexpensive combination of molecular dynamics calculations and a crystal field analysis can be employed to obtain a dynamical picture of the crystal field splitting. We present the time evolution during 500ns of the spin energy levels in a terbium complex. Our calculations evidence an amplitude of up to tens of cm-1 for the oscillations of the spin energy levels in the fs time scale. Crucially, we also see that the oscillations average out and practically disappear at longer time scales, thus ruling out the modulation of spin energy levels by phonons of long wavelength $\lambda$ (up to $\lambda$ = 40 $\AA$). Our results are compatible with the common approximation of focusing on local vibrations, but at the same time highlight the risks of assuming that the spin energy levels are time- and temperature-independent., Comment: 5 pages main text + 7 pages Supporting Information

Published
2018

8. Pomotrelvir and Nirmatrelvir Binding and Reactivity with SARS‐CoV‐2 Main Protease: Implications for Resistance Mechanisms from Computations.

Author

Schillings, Johanna, Ramos‐Guzmán, Carlos A., Ruiz‐Pernía, J. Javier, and Tuñón, Iñaki

Subjects
PERMUTATION groups, QUANTUM mechanics, SECONDARY amines, ANALYTICAL chemistry, TERTIARY amines
Abstract

We investigate the inhibition mechanism between pomotrelvir and the SARS‐CoV‐2 main protease using molecular mechanics and quantum mechanics/molecular mechanics simulations. Alchemical transformations where each Pi group of pomotrelvir was transformed into its counterpart in nirmatrelvir were performed to unravel the individual contribution of each group to the binding and reaction processes. We have shown that while a γ‐lactam ring is preferred at position P1, a δ‐lactam ring is a good alternative for the design of inhibitors for variants presenting mutations at position 166. For the P2 position, tertiary amines are preferred with respect to secondary amines. Flexible side chains at the P2 position can disrupt the preorganization of the active site, favouring the exploration of non‐reactive conformations. The substitution of the P2 group of pomotrelvir by that of nirmatrelvir resulted in a compound, named as C2, that presents a better binding free energy and a higher population of reactive conformations in the Michaelis complex. Analysis of the chemical reaction to form the covalent complex has shown a similar reaction mechanism and activation free energies for pomotrelvir, nirmatrelvir and C2. We hope that these findings could be useful to design better inhibitors to fight present and future variants of the SARS‐CoV‐2 virus. [ABSTRACT FROM AUTHOR]

Published
2024
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29. Impact of SARS-CoV-2 3CL Protease Mutations on Nirmatrelvir Inhibitory Efficiency. Computational Insights into Potential Resistance Mechanisms

Author

Ramos-Guzmán, Carlos A., Andjelkovic, Milorad, Zinovjev, Kirill, Ruiz-Pernía, J. Javier, and Tuñón, Iñaki

Subjects
SARS-CoV-2, main protease, 3CL protease, mutations, QM/MM, free energy
Abstract

The use of antiviral drugs can promote the appearance of mutations in the target protein that increase the resistance of the virus to the treatment. This is also the case of nirmatrelvir, a covalent inhibitor of the 3CL protease of SARS-CoV-2. In this work we show how the by-residue decomposition of noncovalent interactions established between the drug and the enzyme, in combination with an analysis of natural occurring mutations, can be used to detect potential mutations in 3CL protease conferring resistance to nirmatrelvir. We also investigate the consequences of these mutations on the reaction mechanism to form the covalent enzyme-inhibitor complex. In particular, we show that the E166V variant of the protease shows a smaller affinity by nirmatrelvir and a larger activation free energy for the formation of the covalent complex, both factors contributing to an increased resistance to the treatment with this drug. The conclusions derived from our work can be used to anticipate the consequences of the introduction of nirmatrelvir in the fitness landscape of the virus and to design new inhibitors to prevent resistance mechanisms.

Published
2022
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