Ciencia e Ingeniería en Alimentos y Biotecnología
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Item Propuesta de una quimioteca de compuestos relacionados estructuralmente y diseñados para el tratamiento la enfermedad de Huntington(Universidad Técnica de Ambato. Facultad de Ciencia e Ingeniería en Alimentos y Biotecnología. Carrera de Biotecnología, 2024-08) Sanchez Guayta, Kevin Joel; Galarza Galarza, Cristian FernandoHuntington's disease (HD) is an inherited neurodegenerative disorder that affects movement, cognition and behaviour. It is characterised by uncontrollable chorea movements, difficulty speaking and swallowing, memory and thinking problems, and mood swings. HD progresses over time and usually results in death 15-20 years after diagnosis; treatment focuses on controlling symptoms. Medications can help relieve chorea movements, muscle stiffness and psychiatric problems. Physiotherapy and speech therapy may also be helpful. Research into HD is ongoing, with the goal of finding new therapies and, ultimately, a cure. Scientists are using various methods, such as bioinformatics and computer science, to identify genes and proteins that may be involved in the disease. In this study, these methods were used to identify 20 elite genes potentially implicated in HD. The researchers also identified several promising therapeutic targets, including DRD2, PDE10A and CNR1. These findings provide new insights into the molecular basis of HD and may lead to the development of new treatments. HD research is encouraging and there is steady progress towards understanding and treating this devastating disease. Scientists are working hard to find a cure, and with continued support, it is hoped that one day this goal will be achieved.Item Predicción de proteínas de novo mediante inteligencia artificial para la inhibición del factor NF-κB en el cáncer gástrico(Universidad Técnica de Ambato. Facultad de Ciencia e Ingeniería en Alimentos y Biotecnología. Carrera de Biotecnología, 2024-08) Laverde Lomas, Diego Martin; Galarza Galarza, Cristian FernandoIn this research, highlights the limited effectiveness of current treatments for gastric cancer and the role of AI tools in the development of new personalized strategies, through the prediction of de novo proteins aimed at inhibiting the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) associated with this type of cancer. Thirty proteins were predicted, with a similar composition to those stored in standard and experimental databases. Their stability and folding capacity were analyzed based on the energies from intra and intermolecular interactions by molecular dynamics simulations. Furthermore, a molecular docking process was performed between several genes or transcription factors regulated by NF-κB and the predicted proteins, different thermodynamic variables such as Gibbs Free Energy, Dissociation Constant, Enthalpy, Heat Capacity, and Entropy were calculated and compared with respect to the complex of Inhibitor Alpha of kappa B and the protein composed of the p65 and p50 subunits of NF-κB to verify the affinity of their protein-protein interaction and structural conformation state. Finally, the affinity and selectivity of the resulting interactions were evaluated, concluding that the de novo proteins predicted by artificial intelligence are viable for the generation of new treatments and the design of new drugs to treat gastric cancer.Item Identificación de posibles dianas terapéuticas para la Enfermedad de Parkinson mediante la aplicación de métodos in silico(Universidad Técnica de Ambato. Facultad de Ciencia e Ingeniería en Alimentos y Biotecnología. Carrera de Ingeniería Bioquímica, 2024-02) Chimbo Gavilanes, Klever Javier; Galarza Galarza, Cristian FernandoIn the exploration of possible therapeutic targets to treat Parkinson's disease through computational chemistry, drug design using docking tools is employed. This process is based on the analysis of genes such as LRRK2, where the main objective is to identify the most optimal binding sites in terms of energetic stability, considering them as possible ideal locations for protein action. In this context, virtual screening makes it possible to verify whether the complexes formed between the protein and the ligand represent a potential avenue for the investigation of a disease-specific drug. The analysis of several disease databases, such as MalaCards, Harmonizome, KEGG, OMIM, Unitpro, Disgenet, GeneReviews and Orphanet, has allowed the identification of key genes in Parkinson's disease. These genes are of great importance since, among numerous candidates, those with similarities in molecular processes and common dysfunctions were selected. The grouping and categorization of these genes facilitated the creation of a biological network of interactions using Cytoscape, accompanied by a bibliographic investigation of the metabolic pathways and the relationships between them, thanks to this approach, mutations in the LRRK2 gene were identified to then search for possible druggable sites in this molecule, with the aim of forming protein-ligand complexes. Thus, existing drugs or ligands can be analyzed by screening and evaluation of toxicological properties. In this bioinformatics study of therapeutic targets, I point out that the main ligand Losulazine presents a higher affinity of pharmacological interaction with the LRRK2 gene.Item Evaluación de posibles dianas terapéuticas para el cáncer de colon aplicando Pipeline Bioinformático como base para el diseño de fármacos asistido por computador(Universidad Técnica de Ambato. Facultad de Ciencia e Ingeniería en Alimentos y Biotecnología. Carrera de Biotecnología, 2023-09) Jácome Campos, Mario Fabricio; Galarza Galarza, Cristian FernandoColon cancer is a common type of malignant tumor in the gastrointestinal tract, accounting for about 13 percent of all tumors. Its development is influenced by epigenetic changes, genetic and environmental factors. However, current methods for diagnosing and treating this disease are often expensive, making access to treatment difficult for many patients. To identify the genes that are expressed or inhibited in colon cancer, differential expression analysis was performed using R. These genes were contrasted with databases such as: OMIM, Malacards, Harmonizome, and KEGG. The most relevant genes are grouped according to their biochemical alteration, with this information biological interaction networks are created through Cytoscape to identify proteins that are altered within the disease process. For the identification of the targets, the DrugBank database was used, through DoGSiteScorer the drugable sites were identified, virtual screening is performed through MTiopenScreen to find possible ligands that present high binding affinity. The interaction networks obtained from STITCH allow the identification of the drug that is linked to the metabolic pathways to analyze the protein-ligand interactions. The drug etoposide was identified, and its pharmacokinetic and toxicity properties are assessed by bioinformatics predictions using QSAR VEGA and pkCSM models. The toxicity and hepatotoxicity were found to be negative, suggesting that this could be a viable candidate for the development of drugs targeting the SMAD2 and CASP9 genes.Item Identificación de posibles dianas terapéuticas en Alzheimer utilizando pipeline bioinformático combinado para aplicarlas al diseño de fármacos asistidos por computadora(Universidad Técnica de Ambato. Facultad de Ciencia e Ingeniería en Alimentos y Biotecnología. Carrera de Biotecnología, 2023-09) Barriga Sanchez, Luis Leonardo; Galarza Galarza, Cristian FernandoBioinformatics has a potential biotechnological use because it allows the study of genetically complex diseases using different tools. The aim of this project was to analyze transcriptomic data related to Alzheimer's disease (AD) for the identification of potential therapeutic targets and computer-aided drug design. This was done through the application of a multilevel analysis of biological interaction networks, molecular docking, and evaluation of the pharmacokinetic properties of selected drugs. The analyses indicated a total of 507 and 478 genes with high and low expression, respectively, present in brains with different stages of AD. The results of the protein-protein interaction and miRNA-miRNA network analysis identified only one biomarker, hsa-mir-34a-5p, for the diagnosis of AD and asymptomatic AD in cancer patients. Survival analysis revealed that CDK6 and CD44 are potential therapeutic targets for AD. Additionally, the established pipeline also identified CCND1 as another potential therapeutic target. The drug-gene interaction networks reflected four potential drug candidates for repurposing in the treatment of AD: Estradiol, Trichostatin A, Doxorubicin, and Dorsomorphin. Molecular docking demonstrated that Estradiol and Trichostatin A can inhibit the CCND1 protein, while Dorsomorphin induces inhibition of CDK6, because of their free energy of binding is lower than the reference. The evaluation of pharmacokinetic properties indicated that only Trichostatin A can be used for the treatment of AD in humans.Item Búsqueda de posibles dianas terapéuticas para el cáncer papilar de tiroides (PTC)(Universidad Técnica de Ambato. Facultad de Ciencia e Ingeniería en Alimentos y Biotecnología. Carrera de Ingeniería Bioquímica, 2022-09) Lagua Mainato, Christian Orley; Galarza Galarza, Cristian FernandoIn the search for possible therapeutic targets through computational chemistry for papillary thyroid cancer (PTC), the design of drugs with docking tools is based on the analysis of the BRAF gene, where the best binding sites are mainly identified. Regarding energy stability, therefore, the virtual screening allowed to verify the drugability of said complexes that were created between protein and ligand, this represents a potential avenue of research for the development of an optimal and specific drug for said disease. The analysis within the databases of diseases such as MalaCards, Harmonizome, KEGG, OMIM, Unitpro, Disgenet, GeneReviews and Orphanet allowed to know the main genes that lead the carcinogenesis process in PTC, certain genes presented common dysfunctions so that it was possible to group and categorize them to then create a biological network of interaction with the help of Cytoscape and subsequently the metabolic pathways of these genes and the relationship between them were investigated bibliographically. In this way, the mutations that this target gene presents and the alterations in its metabolic pathway were identified. Finally, the mutations that the BRAF gene suffers were found to subsequently identify possible drugable sites that can create protein-ligand complexes, so that the existing drugs currently they were analyzed by screening and subsequent analysis of toxicological properties. Therefore, this bioinformatic study allowed to determine that the ligands Entrectinib, Bms-833923, Afacifenacin, Floxacrine, Olaparib, Nolpitantium, Aleplasinin present pharmacological potential for the BRAF gene.Item Estudios bioinformáticos sobre la proteína Spike del SARS CoV-2 para el desarrollo de posibles inhibidores(Universidad Técnica de Ambato. Facultad de Ciencia e Ingeniería en Alimentos y Biotecnología. Carrera de Ingeniería Bioquímica, 2021-03) Villacis Perez, Nestor Alexander; Terán Mera, David AndrésWith the worldwide alarm of COVID-19 multiple laboratories were dedicated to the search for a vaccine, for these studies it is imperative to work in a laboratory, however, there are ways in which you can contribute to the development of treatments against this disease, one way that is addressed in this project is an in silico analysis, which by molecular docking. Molecular docking was performed with the SARS-CoV-2 Spike protein as a receptor and 13,602 compounds from the CASPeR, ChemBridge and Pathogen Box libraries as ligands. The docking yielded binding affinity (BA) data, results that helped to choose the ligands whose BA was between -6.8 and -5.8 kcal/mol, however, since it was too large a number it was reduced to the 11 best ligands, these were analyzed graphically, so that the distance, number and type of non-covalent interactions were collected. In addition to the BA, the dissociation constant (Kd) was also calculated, which verified that the chosen ligands were able to form interactions that can be taken into account for the development of inhibitors, however, the Kd found are not comparable with the Kd of 14.7 nM that exists between the hACE2 receptor and spike of SARS-CoV-2. Graphical analysis of the 11 ligands revealed that they were able to form highly valuable interactions such as hydrogen bridges, aromatic, hydrophobic and halogen interactions. Interactions with the potential to block the interactions between hACE2 and Spike of SARS-CoV-2, leaving grounds for further studies.Item Cribado virtual de inhibidores de la enzima Mpro del virus SARS-CoV-2 empleando librerías de compuestos y homología estructural con proteasas de virus patógenos de animales(Universidad Técnica de Ambato. Facultad de Ciencia e Ingeniería en Alimentos y Biotecnología. Carrera de Ingeniería Bioquímica, 2021-01) Ramos Aristimbay, María Lisette; García Solís, Mario DanielThe purpose of this study is to perform virtual screening of SARS-CoV-2 virus Mpro enzyme inhibitors using compound libraries and structural homology with animal pathogenic virus proteases. In response to the present pandemic the world is going through, caused by COVID-19, so it is of paramount importance to search for compounds, which prevent the spread of SARS-CoV-2, with which medicines can be made to curb the contagions of this disease. Since the main protease Mpro is responsible for carrying out the proteolytic processes during the replication of the virus, it has been selected as a target for the search for molecules that inhibit its activity, thus preventing the virus from continuing to multiply. For this, a homology analysis was performed that could identify that this protease is preserved in several species of coronavirus that infect animals, such as those that cause murine hepatitis, swine transmissible gastroenteritis, feline peritonitis, and avian infectious bronchitis. Which allowed us to look for compounds used to treat these diseases, and to create a library with the most effective ligands. This was able to determine the druggable sites of the enzyme and perform a molecular coupling (docking), identifying ten inhibitors that best bind to Mpro, including Ritonavir, with which, through subsequent in vitro studies, COVID-19 drugs could be generated, and tested in other coronaviruses with which homology exists.Item Identificación y modelamiento de mutaciones que otorgan resistencia a inhibidores de la enzima ARN polimerasa ARN dependiente del virus SARS-CoV-2(Universidad Técnica de Ambato. Facultad de Ciencia e Ingeniería en Alimentos y Biotecnología. Carrera de Ingeniería Bioquímica, 2021-01) Jaramillo Guapisaca, Karen Andrea; García Solís, Mario DanielThe emergence of a new severe acute respiratory syndrome coronavirus (SARS-CoV-2), of which there is not yet effective treatment, so the SARS-CoV-2 dependent RNA polymerase (RdRp) enzyme, is one of the main goals for developing compounds with antiviral activity. Based on this principle, structural analogues of nucleosides such as Favipiravir, Ribavirin and Remdesivir, particularly, the latter is an effective SARS-CoV-2 RdRp inhibitor and other RNA viruses such as MERS being a major candidate as a therapeutic option for the treatment of COVID-19. Key RdRp residues of the virus, which assist in the junction of Remdesivir that maintain non-covalent interactions, were identified. The degree of conservation of these residues was analyzed by multiple sequence alignment with RdRps. This analysis allowed mutant variants to be modeled in three specific positions of the enzyme's active site, Val557Ile, Ala688Gly and Ser759Thr, and evaluate the effect of these mutations on the binding properties of the inhibitor. Affinity and free energy were determined by molecular coupling in the GOLD program. The results show that all three mutations decrease Remdesivir's theoretical affinity for the active RdRp site. The most harmful mutation for the binding of Remdesivir with the enzyme was the Val557Ile variant with an affinity Score 1.4 times lower than that observed for the native enzyme. These results allow us to foresee the effect of possible changes that may occur in the viral polymerase in a natural way and to generate therapeutic alternatives to counteract the effect of resistance to RdRp inhibitors, such as Remdesivir.Item Estudios bioinformáticos de la enzima convertidora de angiotensina en humanos (hACE2) para el desarrollo de posibles inhibidores contra el SARS-CoV-2(Universidad Técnica de Ambato. Facultad de Ciencia e Ingeniería en Alimentos y Biotecnología. Carrera de Ingeniería Bioquímica, 2021-01) Hoyos Caicedo, Jhoni Javier; Terán Mera, David AndrésThe bioinformatic studies carried out on human angiotensin converting enzyme 2 (hACE2) for the development of possible inhibitors against the SARS-CoV-2 virus, were mainly joint molecular docking. Docking was mainly based on detect interactions between ligands belonging to three libraries. The libraries used were three, CASPeR, ChemBridge and Pathogen Box. From each library, a group of compounds were chosen for docking. From the CASPeR library, the compounds named Drug (3517 ligands) were chosen from the ChemBridge compound library the Fragment Library (10064 ligands) were chosen. Finally, the Pathogen Box compounds (400 ligands), belonging to Medicine for Malaria Venture. The purpose of the present study was to determine the compounds (ligands) that have the potential to be inhibitors of the hACE2 receptor. After analyzing the results by means of binding affinity and intermolecular interactions, 15 ligands with the best interaction were found in the enzyme-ligand complex. These ligands have the potential to be inhibitors of an active site zone, when docking in the amino acids Lysine-31 (Lys-31), Glutamate-35 (Glu-35), Aspartate-38 (Asp-38) and Lysine- 353 (Lys-353). The present study is important since, having carried out docking studies with different ligands, it was possible to obtain those with the best interaction. The results obtained can be used to carry out in vitro and in vivo studies with the virus.