Laboratorio Of Modelado Molecular Y Bioinformatica

Mexico City, Mexico

Laboratorio Of Modelado Molecular Y Bioinformatica

Mexico City, Mexico
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Tolentino-Lopez L.,Laboratorio Of Modelado Molecular Y Bioinformatica | Segura-Cabrera A.,National Polytechnic Institute of Mexico | Reyes-Loyola P.,Laboratorio Of Modelado Molecular Y Bioinformatica | Zimic M.,Cayetano Heredia Peruvian University | And 8 more authors.
Biopolymers | Year: 2013

The recent occurrence of 2009 influenza A (H1N1) pandemic as well as others has raised concern of a far more dangerous outcome should this virus becomes resistant to current drug therapies. The number of clinical cases that are resistant to oseltamivir (Tamiflu®) is larger than the limited number of neuraminidase (NA) mutations (H275Y, N295S, and I223R) that have been identified at the active site and that are associated to oseltamivir resistance. In this study, we have performed a comparative analysis between a set of NAs that have the most representative mutations located outside the active site. The recently crystallized NA-oseltamivir complex (PDB ID: 3NSS) was used as a wild-type structure. After selecting the target NA sequences, their three-dimensional (3D) structure was built using 3NSS as a template by homology modeling. The 3D NA models were refined by molecular dynamics (MD) simulations. The refined models were used to perform a docking study, using oseltamivir as a ligand. Furthermore, the docking results were refined by free-energy analysis using the MM-PBSA method. The analysis of the MD simulation results showed that the NA models reached convergence during the first 10 ns. Visual inspection and structural measures showed that the mutated NA active sites show structural variations. The docking and MM-PBSA results from the complexes showed different binding modes and free energy values. These results suggest that distant mutations located outside the active site of NA affect its structure and could be considered to be a new source of resistance to oseltamivir, which agrees with reports in the clinical literature. © 2012 Wiley Periodicals, Inc. Copyright © 2012 Wiley Periodicals, Inc.

Rosas-Trigueros J.L.,National Polytechnic Institute of Mexico | Ilizaliturri-Flores I.,National Polytechnic Institute of Mexico | Benitez-Cardoza C.G.,National Polytechnic Institute of Mexico | Benitez-Cardoza C.G.,Laboratorio Of Investigacion Bioquimica | And 2 more authors.
Current Medicinal Chemistry | Year: 2012

Bcl-2 (B-cell lymphoma 2) family proteins have been studied intensively due to their association with cancer and other human diseases. These proteins were originally associated with the regulation of outer mitochondrial membrane integrity and apoptosis. However, there is experimental evidence that suggests that several members of this family play instrumental roles in other cellular pathways including autophagy, endoplasmic reticulum signaling, mitochondrial morphology and synaptic activity among others. Bcl-2 family proteins have been explored using diverse experimental and theoretical methods to obtain structural information that can provide valuable insight for drug development. This review is focused on computational studies related to Bcl-2 family proteins. Different strategies are described and evaluated, such as Molecular Dynamics simulations, docking, and rational drug design with the aim of demonstrating the importance of structural details of either ligands or proteins. The relevance of the knowledge obtained using these tools to drug design is discussed. © 2012 Bentham Science Publishers.

Lopez-Martinez M.,Escuela Nacional Ciencias Biologicas | Salgado-Zamora H.,Escuela Nacional Ciencias Biologicas | Campos-Aldrete Ma.E.,Escuela Nacional Ciencias Biologicas | Trujillo-Ferrara J.G.,Laboratorio Of Modelado Molecular Y Bioinformatica | And 2 more authors.
Medicinal Chemistry Research | Year: 2012

A number of imidazo[1,2-a]pyridine derivatives were selected and investigated in relation to antiparasitic (Trichomonas vaginalis) activity. After treatment with derivatives, biological activity was assessed by determination of the in vitro viability of cell cultures, using alamar blue as a metabolic indicator. A good correlation was found between the anti-parasitic activity and the partition coefficient log P determined experimentally on the tested compounds, which explained up to 84% of the measured activity. A favorable interval (0.9 ± 0.3 log P) was found for optimum biological response. © Springer Science+Business Media, LLC 2011.

Acosta-Hernandez M.E.,University of Veracruz | Mancilla-Percino T.,National Polytechnic Institute of Mexico | Correa-Basurto J.,Laboratorio Of Modelado Molecular Y Bioinformatica | Saavedra-Velez M.,University of Xalapas | And 3 more authors.
Archivos de Neurociencias | Year: 2011

Mental disorders are considered a public health problem in most of the world. Depressive disorder, also known as clinical depression is a mental disorder characterized by long periods of sadness, affecting behavior and the thinking of the individual. The occurrence of depression in children and adolescents has increased in the last fifty years. Anyone can experience depression, regardless of age, ethnicity or gender, epidemiological studies indicate that this disorder occurs in about 3-8% of adolescents, whereas in adults occurs in about 4.5% of population. It causes social isolation and can, in severe cases, lead to suicide. Risk factors for depression include: family history, gender, and high stress situations. The diagnostic criteria for depression is well established in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IVTR). A safe and effective treatment requires accurate diagnosis, however, there is the risk of depression in children may be underdiagnosed because some children and adolescents may have difficulty identifying and describing the symptoms. ©INNN, 2011.

Correa-Basurto J.,Laboratorio Of Modelado Molecular Y Bioinformatica | Ramos-Morales F.R.,University of Veracruz | Matus M.H.,University of Veracruz | Rosales-Hernandez M.C.,Laboratorio Of Modelado Molecular Y Bioinformatica | And 3 more authors.
Molecular Simulation | Year: 2012

Topoisomerases (Topos) are very important protein targets for drug design in cancer treatment. Human Topo type II (hTopo II) has been widely studied experimentally and theoretically. Here, we performed protein rigid/flexible side-chain docking to study a set of thirty-nine 3-substituted-2,6- piperazindiones (labelled 1a, (R)-[(2-20)a] and (S)-[(2-20)b]) derived from -amino acids. To explain the ligand-protein complexes at the electronic level [using the highest occupied and the lowest unoccupied molecular orbitals (HOMO and LUMO) energies], density functional theory calculations were carried out. Finally, to show adenosine triphosphate (ATP) binding-site constituents, the Q-SiteFinder program was used. The docking results showed that all of the test compounds bind to the ATP-binding site on hTopo II. Recognition is mediated by the formation of several hydrogen bond acceptors or donators. This site was the largest (631Å 3) according to the Q-SiteFinder program. When using the protein rigid docking protocol, compound 13a derived from (R)-Lys showed the highest affinity. However, when a flexible side-chain docking protocol was used, the compound with the highest affinity was 16a, derived from (R)-Trp. Frontier molecular orbital studies showed that the HOMO of the ligand interacts with the LUMO located at side-chain residues from the protein-binding site. The HOMO of the binding site interacts with the LUMO of the ligand. We conclude that some ligand properties including the hindrance effect, hydrogen bonds, - interactions and stereogenic centres are important for the ligand to be recognised by the ATP-binding site of hTopo II. © 2012 Copyright Taylor and Francis Group, LLC.

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