{"id":{"repo_id":"vt","oai_identifier":"oai:vtechworks.lib.vt.edu:10919/135439"},"canonical_url":"https://search.dev.ndltd.org/etd/vt/oai:vtechworks.lib.vt.edu:10919/135439","repository":{"repo_id":"vt","name":"Virginia Tech","base_url":"https://vtechworks.lib.vt.edu/oai/request"},"display":{"title":"Modeling of Electrostatic Interactions inside Human Voltage-Gated Sodium Channels","abstract":"In this project, we focus on the permeation of Na+ through human voltage-gated sodium channels (Navs). Despite their biological significance, the selective permeation mechanism of Nav channels remains poorly understood at the molecular level. Here, we calculated electric fields inside the channel pore of Nav1.5, 1.6, and 1.7 to gain insights into the components that control the selectivity and permeation of Nav channels. We found that water inside the channel pore aligns vertically in response to the electric fields created by the channel residues. The regions with stronger electric field, characterized by stronger water alignment, correlate to Na+ binding sites identified by Na+ free energy profile. Residues in the P-loop, including the selectivity filter and outer ring residues, generate strong electric fields acting on pore Na+ ions, showing their significance in Na+ binding and permeation. Future study with different ions can identify their roles in ion selectivity. Overall, we have shown that electric fields computed from molecular dynamics simulations using the AMOEBA force field serve as effective indicators for identifying residues crucial to protein function.","abstract_html":"In this project, we focus on the permeation of Na+ through human voltage-gated sodium channels (Navs). Despite their biological significance, the selective permeation mechanism of Nav channels remains poorly understood at the molecular level. Here, we calculated electric fields inside the channel pore of Nav1.5, 1.6, and 1.7 to gain insights into the components that control the selectivity and permeation of Nav channels. We found that water inside the channel pore aligns vertically in response to the electric fields created by the channel residues. The regions with stronger electric field, characterized by stronger water alignment, correlate to Na+ binding sites identified by Na+ free energy profile. Residues in the P-loop, including the selectivity filter and outer ring residues, generate strong electric fields acting on pore Na+ ions, showing their significance in Na+ binding and permeation. Future study with different ions can identify their roles in ion selectivity. Overall, we have shown that electric fields computed from molecular dynamics simulations using the AMOEBA force field serve as effective indicators for identifying residues crucial to protein function.","abstract_has_math":false,"creators":["Chen, Taoyi"],"institution":"Virginia Tech","degree_name":"Master of Science","degree_level":"masters","degree_discipline":"Chemistry","degree_department":"Chemistry","school":null,"contributors":[],"advisors":[],"committee_chairs":["Welborn, Valerie"],"committee_members":["Lemkul, Justin Alan","Mayhall, Nicholas","Crawford, Daniel"],"year":2025,"date_issued":"2025-06-09","date_published":"2025-06-09","updated_at":"2026-07-22T22:19:01Z","subjects":["Human Sodium Channel","Molecular Dynamics","Electric Field","Polarizable Force field","Water Dynamics"],"languages":["en"],"rights":["In Copyright"],"rights_urls":["http://rightsstatements.org/vocab/InC/1.0/"],"identifier_entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["vt_gsexam:44027"],"render_values":[{"text":"vt_gsexam:44027","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/10919/135439","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.committeechair","label":"Committee Chair","values":["Welborn, Valerie"]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Lemkul, Justin Alan","Mayhall, Nicholas","Crawford, Daniel"]},{"key":"dc:contributor.department","label":"Department","values":["Chemistry"]},{"key":"dc:creator","label":"Author","values":["Chen, Taoyi"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-06-10T08:03:05Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-06-10T08:03:05Z"]},{"key":"dc:date.issued","label":"Date","values":["2025-06-09"]},{"key":"dc:publisher","label":"Institution","values":["Virginia Tech"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["masters"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Virginia Polytechnic Institute and State University"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Human Sodium Channel","Molecular Dynamics","Electric Field","Polarizable Force field","Water Dynamics"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["In Copyright"]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://rightsstatements.org/vocab/InC/1.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["vt_gsexam:44027"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/10919/135439"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["In this project, we focus on the permeation of Na+ through human voltage-gated sodium channels (Navs). Despite their biological significance, the selective permeation mechanism of Nav channels remains poorly understood at the molecular level. Here, we calculated electric fields inside the channel pore of Nav1.5, 1.6, and 1.7 to gain insights into the components that control the selectivity and permeation of Nav channels. We found that water inside the channel pore aligns vertically in response to the electric fields created by the channel residues. The regions with stronger electric field, characterized by stronger water alignment, correlate to Na+ binding sites identified by Na+ free energy profile. Residues in the P-loop, including the selectivity filter and outer ring residues, generate strong electric fields acting on pore Na+ ions, showing their significance in Na+ binding and permeation. Future study with different ions can identify their roles in ion selectivity. Overall, we have shown that electric fields computed from molecular dynamics simulations using the AMOEBA force field serve as effective indicators for identifying residues crucial to protein function."]},{"key":"dc:description.abstractgeneral","label":"General Abstract","values":["Voltage-gated sodium channels are essential proteins in nerve and muscle cells that transmit electrical signals. They allow Na+ to flow into the cell while rejecting other ions. Understanding the selective permeation process of these channels is crucial. In this study, we used molecular dynamics simulations to explore the electrostatic environment inside the channel pore. Our simulations reveal that water molecules align inside the channel pore. This alignment is the reaction of water dipoles to the electric fields generated by the channels' residues. We show that these residues have been shown to dictate the selective permeation process. Previous experimental alternations of these residues show disruption of channel functions, indicating their importance. The free energy profiles of Na+ along the channel pore revealed multiple Na+ binding sites situated in regions of stronger electric fields, corresponding to those residues of importance. Overall, we demonstrated that electric field can be used as an indicator for identifying key residues for protein function."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Master of Science"]},{"key":"dc:format.medium","label":"Dc Format Medium","values":["ETD"]},{"key":"dc:title","label":"Title","values":["Modeling of Electrostatic Interactions inside Human Voltage-Gated Sodium Channels"]}]}],"canonical_facts":{"dc:contributor.committeechair":["Welborn, Valerie"],"dc:contributor.committeemember":["Lemkul, Justin Alan","Mayhall, Nicholas","Crawford, Daniel"],"dc:contributor.department":["Chemistry"],"dc:creator":["Chen, Taoyi"],"dc:date.accessioned":["2025-06-10T08:03:05Z"],"dc:date.available":["2025-06-10T08:03:05Z"],"dc:date.issued":["2025-06-09"],"dc:description.abstract":["In this project, we focus on the permeation of Na+ through human voltage-gated sodium channels (Navs). Despite their biological significance, the selective permeation mechanism of Nav channels remains poorly understood at the molecular level. Here, we calculated electric fields inside the channel pore of Nav1.5, 1.6, and 1.7 to gain insights into the components that control the selectivity and permeation of Nav channels. We found that water inside the channel pore aligns vertically in response to the electric fields created by the channel residues. The regions with stronger electric field, characterized by stronger water alignment, correlate to Na+ binding sites identified by Na+ free energy profile. Residues in the P-loop, including the selectivity filter and outer ring residues, generate strong electric fields acting on pore Na+ ions, showing their significance in Na+ binding and permeation. Future study with different ions can identify their roles in ion selectivity. Overall, we have shown that electric fields computed from molecular dynamics simulations using the AMOEBA force field serve as effective indicators for identifying residues crucial to protein function."],"dc:description.abstractgeneral":["Voltage-gated sodium channels are essential proteins in nerve and muscle cells that transmit electrical signals. They allow Na+ to flow into the cell while rejecting other ions. Understanding the selective permeation process of these channels is crucial. In this study, we used molecular dynamics simulations to explore the electrostatic environment inside the channel pore. Our simulations reveal that water molecules align inside the channel pore. This alignment is the reaction of water dipoles to the electric fields generated by the channels' residues. We show that these residues have been shown to dictate the selective permeation process. Previous experimental alternations of these residues show disruption of channel functions, indicating their importance. The free energy profiles of Na+ along the channel pore revealed multiple Na+ binding sites situated in regions of stronger electric fields, corresponding to those residues of importance. Overall, we demonstrated that electric field can be used as an indicator for identifying key residues for protein function."],"dc:description.degree":["Master of Science"],"dc:format.medium":["ETD"],"dc:identifier.other":["vt_gsexam:44027"],"dc:identifier.uri":["https://hdl.handle.net/10919/135439"],"dc:language.iso":["en"],"dc:publisher":["Virginia Tech"],"dc:rights":["In Copyright"],"dc:rights.uri":["http://rightsstatements.org/vocab/InC/1.0/"],"dc:subject":["Human Sodium Channel","Molecular Dynamics","Electric Field","Polarizable Force field","Water Dynamics"],"dc:title":["Modeling of Electrostatic Interactions inside Human Voltage-Gated Sodium Channels"],"dc:type":["Thesis"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["masters"],"thesis:degree_name":["Master of Science"],"thesis:institution_name":["Virginia Polytechnic Institute and State University"]},"updated_at":"2026-07-22T22:19:01Z"}