Dr. Juvenal Yosa Reyes
PUBLICATIONS
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JUVENAL YOSA REYES, LEONARDO R LAREO, MARIO BLANCO, ORLANDO EMILIO ACEVEDO SARMIENTO, "Molecular Orbital Differentiation of Agonist and Antagonist Activity in the GlycineB-iGluR-NMDA Receptor". European Journal Of Medicinal Chemistry. 44 ,7 p.2960 .
We present various molecular electronic descriptors of agonists and antagonists for GlycineB-iGluR-NMDA receptor with a view to identify computational measures that help differentiate between these two classes of biologically active compounds. We use as reference the glycine site in the NR1 subunit of the NMDA receptor (GlycineB-iGluR-NMDA). GlycineB-iGluR-NMDA receptor is important in learning and memory, and it is involved in various neurodegenerative diseases such as Alzheimer, Parkinson, and Huntington as well as in neuropathies such as schizophrenia and depression. We carried out quantum calculations at two levels, (1) B3LYP Density Functional (6-311G**), and (2) PM3 Hamiltonian for 168 molecules, of which 22 are agonists and 146 are antagonists. Regardless of the quantum mechanical level used we found a consistent signature of agonists versus antagonist action, the energy of the lowest unoccupied molecular orbital (LUMO). Effective differentiation of agonists and antagonists by a single molecular descriptor is seldom seen. We present a plausible electronic structure argument to rationalize these results.
Juvenal Yosa Reyes and Markus Meuwly, Vibrationally Induced Dissociation of Sulfuric Acid (H2SO4).
J. Phys. Chem. A. 2011. 115, 50. pp 14350.
One of the important reactive steps in Earth’s atmosphere is the decomposition of H2SO4 to H2O and SO3. However, because the UV spectrum of H2SO4 was not found up to 140 nm, alternative mechanisms, including vibrationally induced dissociation, were proposed. Using adiabatic reactive molecular dynamics (ARMD) simulations with validated force fields for the product and educt channels, it is shown through explicit atomistic simulation that by exciting the ν9 (OH-stretching-) mode, photodissociation can occur on the picosecond time scale. With the potential energy surfaces used in the present work, ν9 = 4 is sufficient for this process. From a statistically significant number of trajectories (several thousands), vibrationally induced dissociation times are found to follow Gamma-distributions with most likely reaction times between 40 and 200 ps by depositing energies ranging from 40 to 60 kcal/mol, corresponding to 4 and 6 vibrational quanta in the OH stretching vibration. Because ARMD simulations allow multiple and long-time simulations, both nonstatistical, impulsive H-transfer and statistical, IVR-regimes of the decomposition reaction can be discussed in detail at an atomistic level.
Juvenal Yosa Reyes, Diana Clavijo, Carlos Estevez, Orlando Acevedo Y Leonardo Lareo. Métodos semiempíricos para la evaluación rápida de orbitales frontera en la clasificación de agonistas y antagonistas de la subunidad NR1 de los receptores iGluR-NMDA. Universitas Scientiarium. Univ. Sci. vol.16 no.1 Bogotá Jan./Apr. 2011
The ionotropic glutamate receptors activated by N-Methyl-D-Aspartate (iGluR-NMDA) are of great importance in pharmacology since they are involved in neurodegenerative and neuropsychiatric disorders; they even participate in processes such as synaptic plasticity that are essential for memory formation. Subunit NR1 iGluRs-NMDA is of paramount importance for the appropriate activation of this type of receptors; in fact, many of the pharmaceutical products studied for the abovementioned disorders are targeted specifically to the NR1 subunit. Previous studies have shown that the lowest energy unoccupied molecular orbital (LUMO) can be used as a parameter to estimate the agonist and antagonist activity of the NR1subunit. Objective. Evaluate the semiemprical method CNDO for the rapid calculation of the LUMO energy with the aim of preparing a simple model for the in silico design of new pharmacological substances. Materials and methods. 168 molecules with agonist and antagonist activity in the NR1 subunit were selected. Energy of each structure was optimized and then we calculated the energy of the frontier orbital, the LogP, total energy, capacity of forming hydrogen bonds, binding energy, and dipolar moment. Results. We demonstrate that LUMO energy is enough for discriminating agonist and antagonist molecules of the NR1 subunit and that the CNDO method evaluates these properties in a rapid and efficient way. Conclusions. The CNDO method facilitates a rapid calculation, enabling a future development of effective procedures for the characterization of potential pharmacological substances acting on this particular site.
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Ángela Peña1, Juvenal Yosa, Yesid Cuesta-Astroz, Orlando Acevedo, Leonardo Lareo, Felipe García-Vallejo. Influence of Mg2+ ions on the interaction between 3,5-dicaffeoylquinic acid and HTLV-I integraseUniversitas Scientiarium. Univ. Sci. vol.17 no.1 Bogotá Jan./Apr. 2012.
Objective. Using molecular simulation, we studied the influence of Mg2+ ions on the binding mode of HTLV-I Integrase (IN) catalytic domain (modeled by homology) with the 3,5- Dicaffeoylquinic Acid (DCQA). HTLV-I Integrase homology model was built using template-like crystallographic data of the IN catalytic domain solved for Avian Sarcoma Virus (VSA, pdb: 1VSD). Materials and methods. In order to analyze the role of Mg2+ in the interaction or coupling between 3,5-DCQA and Integrase, three models were created: i) in the absence of Mg2+ ions, ii) with a Mg2+ ion coordinated at Asp15 and Asp72 and iii) model with two Mg2+ ions coordinated at Asp15-Asp72 and Asp72-Glu108. Coupling force and binding free energy between 3,5-DCQA and HTLV-I IN were assessed in the three models. Results. The lowest docking score and free energy binding were obtained for the second model. Mg2+ ion strongly affected the coupling of the inhibitor 3,5-DCQA with HTLV-I catalytic domain of Integrase, thus revealing a strong interaction in the ligand-protein complex regardless of the ligand-catalytic interaction sites for all three models. Conclusion. Altogether, these results strengthen the hypothesis that the presence of one Mg2+ ion could enhance the interaction in the complex by decreasing free energy, therefore increasing the affinity. Moreover, we propose 3,5-DCQA as an important pharmacophore in the rational design of new antiretroviral drugs.
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Xin Tong, Tibor Nagy, Juvenal Yosa Reyes, Matthias Germann, Markus Meuwly & Stefan Willitsch. State-selected ion–molecule reactions with Coulomb-crystallized molecular ions in traps. Chemical Physics Letters. Volume 547, 21 September 2012, Pages 1–8
State-selected Coulomb-crystallized molecular ions were employed for the first time in ion–molecule reaction studies using the prototypical charge-transfer process View the MathML source as an example. By preparing the reactant ions in a well-defined rovibrational state and localizing them in space by sympathetic cooling to milliKelvin temperatures in an ion trap, state- and energy-controlled reaction experiments with sensitivities on the level of single ions were performed. The experimental results were interpreted with quasi-classical trajectory simulations on a six-dimensional potential-energy surface which provided detailed insight into translation-to-rotation energy transfer occurring during charge transfer between N2 and View the MathML source.
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Pierre-André Cazade, Jing Huang, Juvenal Yosa, Jaroslaw J. Szymczak & Markus Meuwly. Atomistic simulations of reactive processes in the gas- and condensed-phase. International Reviews In Physical Chemistry v.31, 2 p.236,2012.
This review focuses on force-field-based approaches to investigate - through computer simulations - reactive processes in chemical and biological systems. Both, reactions in the gas-phase and in condensed-phase environments are discussed and opportunities and the potential for further developments are pointed out. Where available, results are compared with alternative methods and the advantages and drawbacks of the methods are compared. Particular applications include vibrationally and electronically induced (photo)dissociation of small molecules, proton transfer in the gas- and condensed phase and ligand un- and re-binding in proteins.
POSTERS
Tibor Nagy, Juvenal Yosa Reyes, and Markus Meuwly. Multisurface Adiabatic Reactive Molecular Dynamics. DOI: 10.1021/ct400953f
Adiabatic reactive molecular dynamics (ARMD) simulation method isa surface-crossing algorithm for modeling chemical reactions inclassical molecular dynamics simulations using empirical forcefields. As the ARMD Hamiltonian is time dependent during crossing,it allows only approximate energy conservation. In the current work,the range of applicability of conventional ARMD is explored, anda new multisurface ARMD (MS-ARMD) method is presented, implementedin CHARMM and applied to the vibrationally induced photodissociationof sulfuric acid (H2SO4) in the gas phase. For this, an accurate globalpotential energy surface (PES) involving 12 H2SO4 and 4 H2O + SO3 forcefields fitted to MP2/6-311G++(2d,2p) reference energies is employed. TheMS-ARMD simulations conserve total energy and feature both intramolecularH-transfer reactions and water elimination. An analytical treatment ofthe dynamics in the crossing region finds that conventional ARMD canapproximately conserve total energy for limiting cases. In one of them,the reduced mass of the system is large, which often occurs forsimulations of solvated biomolecular systems. On the other hand,MS-ARMD is a general approach for modeling chemical reactionsincluding gas-phase, homogeneous, heterogeneous, and enzymaticcatalytic reactions while conserving total energy in atomistic simulations.
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