{"id":{"repo_id":"brazil-ufpb","oai_identifier":"oai:repositorio.ufpb.br:123456789/559"},"canonical_url":"https://search.dev.ndltd.org/etd/brazil-ufpb/oai:repositorio.ufpb.br:123456789/559","repository":{"repo_id":"brazil-ufpb","name":"Brazil UFPB","base_url":"https://repositorio.ufpb.br/oai/request"},"display":{"title":"Estudo de modelagem molecular de derivados de desoxiuridina como inibidores da dUTPase de Plasmodium falciparum.","abstract":"Malaria is a parasitic disease that continues to b e responsible for a huge number of deaths around the world. The disease is p resent in 99 countries with the alarming number of deaths per year reaching 655,000 ; about 3.3 billion people are at risk areas. Among the agents that cause malaria, Plasmodium falciparum causes the most severe cases, being responsible for about 90% of deaths from this disease. Currently available treatments include the drugs ch loroquine, primaquine, artemisinin and lumefantrine. However, due to its indiscriminat e use for years, parasite resistance to these treatments has become a big pro blem. The enzyme deoxyuridine triphosphate nucleotidohydrolase (dUTPase) of Plasm odium falciparum (EC 3.6.1.23) was chosen as the molecular target for th is study. We produced a complete structural model of Pf dUTPase (PDB ID: 1VYQ) by homology modeling, since the crystal structure stored in the Protein Data Bank s hows regions of undetermined conformation. In this work we used, in addition to conventional molecular dynamics, the Steered Molecular Dynamics technique to simulat e the unbinding process of four deoxyuridine derivatives acting as Pf dUTPase inhibitors. For this purpose, we adopted the external steering force of 0,2 kcal/mol /Å 2 at a constant velocity of 0,02 Å/ps. Hydrogen bonds are formed between the ligand and the residue Ile117 up to 90% of the trajectory. The water molecule of the ac tive site obtained Hbond results up to 68%. The force profiles of the SMD calculatio ns showed linear correlation coefficient R 2 of 0.96 with the Ki experimental data. Our results show quantitatively that the residue Ile117 is the main responsible for the anchoring of the ligands in the active site.","abstract_html":"Malaria is a parasitic disease that continues to b e responsible for a huge number of deaths around the world. The disease is p resent in 99 countries with the alarming number of deaths per year reaching 655,000 ; about 3.3 billion people are at risk areas. Among the agents that cause malaria, Plasmodium falciparum causes the most severe cases, being responsible for about 90% of deaths from this disease. Currently available treatments include the drugs ch loroquine, primaquine, artemisinin and lumefantrine. However, due to its indiscriminat e use for years, parasite resistance to these treatments has become a big pro blem. The enzyme deoxyuridine triphosphate nucleotidohydrolase (dUTPase) of Plasm odium falciparum (EC 3.6.1.23) was chosen as the molecular target for th is study. We produced a complete structural model of Pf dUTPase (PDB ID: 1VYQ) by homology modeling, since the crystal structure stored in the Protein Data Bank s hows regions of undetermined conformation. In this work we used, in addition to conventional molecular dynamics, the Steered Molecular Dynamics technique to simulat e the unbinding process of four deoxyuridine derivatives acting as Pf dUTPase inhibitors. For this purpose, we adopted the external steering force of 0,2 kcal/mol /Å 2 at a constant velocity of 0,02 Å/ps. Hydrogen bonds are formed between the ligand and the residue Ile117 up to 90% of the trajectory. The water molecule of the ac tive site obtained Hbond results up to 68%. The force profiles of the SMD calculatio ns showed linear correlation coefficient R 2 of 0.96 with the Ki experimental data. Our results show quantitatively that the residue Ile117 is the main responsible for the anchoring of the ligands in the active site.","abstract_has_math":false,"creators":["Figueirêdo, Felipe Nóbrega Sousa de"],"institution":"Universidade Federal da Paraíba","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014-07-15","date_published":"2014-07-15","updated_at":"2026-07-24T01:17:57Z","subjects":["Malária","dUTpase","Modelagem homologia","Steered molecular Dynamies"],"languages":["pt"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://repositorio.ufpb.br/jspui/handle/123456789/559","outbound_label":"Repository record","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Figueirêdo, Felipe Nóbrega Sousa de"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2014-07-15T11:16:48Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2014-07-15T11:16:48Z"]},{"key":"dc:date.issued","label":"Date","values":["2014-07-15"]},{"key":"dc:publisher","label":"Institution","values":["Universidade Federal da Paraíba"]},{"key":"dc:type","label":"Dc Type","values":["TCC"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Malária","dUTpase","Modelagem homologia","Steered molecular Dynamies"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["pt"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://repositorio.ufpb.br/jspui/handle/123456789/559"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Malaria is a parasitic disease that continues to b e responsible for a huge number of deaths around the world. The disease is p resent in 99 countries with the alarming number of deaths per year reaching 655,000 ; about 3.3 billion people are at risk areas. Among the agents that cause malaria, Plasmodium falciparum causes the most severe cases, being responsible for about 90% of deaths from this disease. Currently available treatments include the drugs ch loroquine, primaquine, artemisinin and lumefantrine. However, due to its indiscriminat e use for years, parasite resistance to these treatments has become a big pro blem. The enzyme deoxyuridine triphosphate nucleotidohydrolase (dUTPase) of Plasm odium falciparum (EC 3.6.1.23) was chosen as the molecular target for th is study. We produced a complete structural model of Pf dUTPase (PDB ID: 1VYQ) by homology modeling, since the crystal structure stored in the Protein Data Bank s hows regions of undetermined conformation. In this work we used, in addition to conventional molecular dynamics, the Steered Molecular Dynamics technique to simulat e the unbinding process of four deoxyuridine derivatives acting as Pf dUTPase inhibitors. For this purpose, we adopted the external steering force of 0,2 kcal/mol /Å 2 at a constant velocity of 0,02 Å/ps. Hydrogen bonds are formed between the ligand and the residue Ile117 up to 90% of the trajectory. The water molecule of the ac tive site obtained Hbond results up to 68%. The force profiles of the SMD calculatio ns showed linear correlation coefficient R 2 of 0.96 with the Ki experimental data. Our results show quantitatively that the residue Ile117 is the main responsible for the anchoring of the ligands in the active site."]},{"key":"dc:title","label":"Title","values":["Estudo de modelagem molecular de derivados de desoxiuridina como inibidores da dUTPase de Plasmodium falciparum."]}]}],"canonical_facts":{"dc:creator":["Figueirêdo, Felipe Nóbrega Sousa de"],"dc:date.accessioned":["2014-07-15T11:16:48Z"],"dc:date.available":["2014-07-15T11:16:48Z"],"dc:date.issued":["2014-07-15"],"dc:description.abstract":["Malaria is a parasitic disease that continues to b e responsible for a huge number of deaths around the world. The disease is p resent in 99 countries with the alarming number of deaths per year reaching 655,000 ; about 3.3 billion people are at risk areas. Among the agents that cause malaria, Plasmodium falciparum causes the most severe cases, being responsible for about 90% of deaths from this disease. Currently available treatments include the drugs ch loroquine, primaquine, artemisinin and lumefantrine. However, due to its indiscriminat e use for years, parasite resistance to these treatments has become a big pro blem. The enzyme deoxyuridine triphosphate nucleotidohydrolase (dUTPase) of Plasm odium falciparum (EC 3.6.1.23) was chosen as the molecular target for th is study. We produced a complete structural model of Pf dUTPase (PDB ID: 1VYQ) by homology modeling, since the crystal structure stored in the Protein Data Bank s hows regions of undetermined conformation. In this work we used, in addition to conventional molecular dynamics, the Steered Molecular Dynamics technique to simulat e the unbinding process of four deoxyuridine derivatives acting as Pf dUTPase inhibitors. For this purpose, we adopted the external steering force of 0,2 kcal/mol /Å 2 at a constant velocity of 0,02 Å/ps. Hydrogen bonds are formed between the ligand and the residue Ile117 up to 90% of the trajectory. The water molecule of the ac tive site obtained Hbond results up to 68%. The force profiles of the SMD calculatio ns showed linear correlation coefficient R 2 of 0.96 with the Ki experimental data. Our results show quantitatively that the residue Ile117 is the main responsible for the anchoring of the ligands in the active site."],"dc:identifier.uri":["https://repositorio.ufpb.br/jspui/handle/123456789/559"],"dc:language.iso":["pt"],"dc:publisher":["Universidade Federal da Paraíba"],"dc:subject":["Malária","dUTpase","Modelagem homologia","Steered molecular Dynamies"],"dc:title":["Estudo de modelagem molecular de derivados de desoxiuridina como inibidores da dUTPase de Plasmodium falciparum."],"dc:type":["TCC"]},"updated_at":"2026-07-24T01:17:57Z"}