{"id":{"repo_id":"ku","oai_identifier":"oai:kuscholarworks.ku.edu:1808/35904"},"canonical_url":"https://search.dev.ndltd.org/etd/ku/oai:kuscholarworks.ku.edu:1808/35904","repository":{"repo_id":"ku","name":"University of Kansas","base_url":"https://kuscholarworks.ku.edu/server/oai/request"},"display":{"title":"Dynamic Molecular Mechanisms and Drug Design of Important Therapeutic Targets","abstract":"Membrane proteins, such as G protein-coupled receptors (GPCRs), and soluble proteins play critical roles in a wide range of physiological and pathological cellular processes. GPCRs constitute the largest family of drug targets. The CXCR4 chemokine receptor, in particular, helps promote HIV entry into host cells. Polycystin-1 (PC1) is an atypical GPCR with 11 transmembrane domains. Mutations in the PC1 protein are responsible for the majority cases of a potentially lethal human autosomal dominant polycystic kidney disease (ADPKD). Moreover, small ubiquitin-like modifiers (SUMO) play an important role in regulation of post-translational modifications. Alterations in the SUMO E1 enzymes is linked to life-threatening neurogenerative disorders, viral infections and cancers. Gaussian accelerated molecular dynamics (GaMD) has been successful in simulating complex biological processes including ligand binding, protein-protein/membrane/nucleic acid interactions, protein folding and GPCR activation. Additionally, Ligand GaMD (LiGaMD) and Peptide GaMD (Pep-GaMD) methods were further developed to model ligand and peptide binding/unbinding, respectively, through improved enhanced sampling. Here, molecular mechanisms of small molecule and peptide mediated activation of important therapeutic targets have been uncovered using powerful computational techniques (including GaMD, LiGaMD, Pep-GaMD, molecular docking and homology modeling) and collaborative experiments.","abstract_html":"Membrane proteins, such as G protein-coupled receptors (GPCRs), and soluble proteins play critical roles in a wide range of physiological and pathological cellular processes. GPCRs constitute the largest family of drug targets. The CXCR4 chemokine receptor, in particular, helps promote HIV entry into host cells. Polycystin-1 (PC1) is an atypical GPCR with 11 transmembrane domains. Mutations in the PC1 protein are responsible for the majority cases of a potentially lethal human autosomal dominant polycystic kidney disease (ADPKD). Moreover, small ubiquitin-like modifiers (SUMO) play an important role in regulation of post-translational modifications. Alterations in the SUMO E1 enzymes is linked to life-threatening neurogenerative disorders, viral infections and cancers. Gaussian accelerated molecular dynamics (GaMD) has been successful in simulating complex biological processes including ligand binding, protein-protein/membrane/nucleic acid interactions, protein folding and GPCR activation. Additionally, Ligand GaMD (LiGaMD) and Peptide GaMD (Pep-GaMD) methods were further developed to model ligand and peptide binding/unbinding, respectively, through improved enhanced sampling. Here, molecular mechanisms of small molecule and peptide mediated activation of important therapeutic targets have been uncovered using powerful computational techniques (including GaMD, LiGaMD, Pep-GaMD, molecular docking and homology modeling) and collaborative experiments.","abstract_has_math":false,"creators":["Pawnikar, Shristi"],"institution":"University of Kansas","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Miao, Yinglong"],"committee_chairs":[],"committee_members":[],"year":2023,"date_issued":"2023-05-31","date_published":"2023-05-31","updated_at":"2026-07-24T02:44:44Z","subjects":["Computational chemistry","drug design","enhanced sampling","GPCRs","molecular dynamics","peptide agonists","small-molecule"],"languages":["en"],"rights":["Copyright held by the author."],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["http://dissertations.umi.com/ku:19005"],"render_values":[{"text":"http://dissertations.umi.com/ku:19005","href":"http://dissertations.umi.com/ku:19005","code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/1808/35904","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Miao, Yinglong"]},{"key":"dc:creator","label":"Author","values":["Pawnikar, Shristi"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-02-10T18:00:09Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-02-10T18:00:09Z"]},{"key":"dc:date.issued","label":"Date","values":["2023-05-31"]},{"key":"dc:publisher","label":"Institution","values":["University of Kansas"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Computational chemistry","drug design","enhanced sampling","GPCRs","molecular dynamics","peptide agonists","small-molecule"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright held by the author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["http://dissertations.umi.com/ku:19005"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/1808/35904"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Membrane proteins, such as G protein-coupled receptors (GPCRs), and soluble proteins play critical roles in a wide range of physiological and pathological cellular processes. GPCRs constitute the largest family of drug targets. The CXCR4 chemokine receptor, in particular, helps promote HIV entry into host cells. Polycystin-1 (PC1) is an atypical GPCR with 11 transmembrane domains. Mutations in the PC1 protein are responsible for the majority cases of a potentially lethal human autosomal dominant polycystic kidney disease (ADPKD). Moreover, small ubiquitin-like modifiers (SUMO) play an important role in regulation of post-translational modifications. Alterations in the SUMO E1 enzymes is linked to life-threatening neurogenerative disorders, viral infections and cancers. Gaussian accelerated molecular dynamics (GaMD) has been successful in simulating complex biological processes including ligand binding, protein-protein/membrane/nucleic acid interactions, protein folding and GPCR activation. Additionally, Ligand GaMD (LiGaMD) and Peptide GaMD (Pep-GaMD) methods were further developed to model ligand and peptide binding/unbinding, respectively, through improved enhanced sampling. Here, molecular mechanisms of small molecule and peptide mediated activation of important therapeutic targets have been uncovered using powerful computational techniques (including GaMD, LiGaMD, Pep-GaMD, molecular docking and homology modeling) and collaborative experiments."]},{"key":"dc:title","label":"Title","values":["Dynamic Molecular Mechanisms and Drug Design of Important Therapeutic Targets"]}]}],"canonical_facts":{"dc:contributor.advisor":["Miao, Yinglong"],"dc:creator":["Pawnikar, Shristi"],"dc:date.accessioned":["2025-02-10T18:00:09Z"],"dc:date.available":["2025-02-10T18:00:09Z"],"dc:date.issued":["2023-05-31"],"dc:description.abstract":["Membrane proteins, such as G protein-coupled receptors (GPCRs), and soluble proteins play critical roles in a wide range of physiological and pathological cellular processes. GPCRs constitute the largest family of drug targets. The CXCR4 chemokine receptor, in particular, helps promote HIV entry into host cells. Polycystin-1 (PC1) is an atypical GPCR with 11 transmembrane domains. Mutations in the PC1 protein are responsible for the majority cases of a potentially lethal human autosomal dominant polycystic kidney disease (ADPKD). Moreover, small ubiquitin-like modifiers (SUMO) play an important role in regulation of post-translational modifications. Alterations in the SUMO E1 enzymes is linked to life-threatening neurogenerative disorders, viral infections and cancers. Gaussian accelerated molecular dynamics (GaMD) has been successful in simulating complex biological processes including ligand binding, protein-protein/membrane/nucleic acid interactions, protein folding and GPCR activation. Additionally, Ligand GaMD (LiGaMD) and Peptide GaMD (Pep-GaMD) methods were further developed to model ligand and peptide binding/unbinding, respectively, through improved enhanced sampling. Here, molecular mechanisms of small molecule and peptide mediated activation of important therapeutic targets have been uncovered using powerful computational techniques (including GaMD, LiGaMD, Pep-GaMD, molecular docking and homology modeling) and collaborative experiments."],"dc:identifier.other":["http://dissertations.umi.com/ku:19005"],"dc:identifier.uri":["https://hdl.handle.net/1808/35904"],"dc:language.iso":["en"],"dc:publisher":["University of Kansas"],"dc:rights":["Copyright held by the author."],"dc:subject":["Computational chemistry","drug design","enhanced sampling","GPCRs","molecular dynamics","peptide agonists","small-molecule"],"dc:title":["Dynamic Molecular Mechanisms and Drug Design of Important Therapeutic Targets"],"dc:type":["Dissertation"]},"updated_at":"2026-07-24T02:44:44Z"}