{"id":1169860,"date":"2026-04-27T11:16:51","date_gmt":"2026-04-27T18:16:51","guid":{"rendered":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/publication\/improving-the-estimation-of-pka-values-for-all-titratable-amino-acids-at-the-water-membrane-interface\/"},"modified":"2026-05-08T14:59:41","modified_gmt":"2026-05-08T21:59:41","slug":"improving-the-estimation-of-pka-values-for-all-titratable-amino-acids-at-the-water-membrane-interface","status":"publish","type":"msr-research-item","link":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/publication\/improving-the-estimation-of-pka-values-for-all-titratable-amino-acids-at-the-water-membrane-interface\/","title":{"rendered":"Improving the Estimation of p K a Values for All Titratable Amino Acids at the Water\/Membrane Interface"},"content":{"rendered":"<p>Understanding how pH-sensitive molecules behave when incorporated into lipid bilayers is a challenging problem that requires specialized methods and robust sampling. Techniques based on constant-pH molecular dynamics (CpHMD) can be employed to investigate the effects of pH on molecules at the water-membrane interface. Here, we compare the performance of enhanced sampling protocols coupled with CpHMD in describing protonation and p<i>K<\/i><sub>a<\/sub>\u00a0values of model Ala pentapeptide systems inserting into a DMPC membrane. From regular CpHMD, replica exchange (pHRE), and umbrella sampling (US-CpHMD), the latter provides more reliable and complete p<i>K<\/i><sub>a<\/sub>\u00a0profiles along bilayer insertion, in particular, at deeper regions of the membrane. Overall, there is a consistent trend for p<i>K<\/i><sub>a<\/sub>\u00a0values to shift toward the molecules\u2019 neutral state, a crucial effect that enables a (de)protonation-assisted increase in membrane permeability. Building on US-CpHMD, we have successfully coupled an umbrella replica exchange scheme (REUS), which significantly improved the reliability of results for our Asp pentapeptide by enhancing configurational sampling between the umbrellas, albeit at a substantial computational cost.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Understanding how pH-sensitive molecules behave when incorporated into lipid bilayers is a challenging problem that requires specialized methods and robust sampling. Techniques based on constant-pH molecular dynamics (CpHMD) can be employed to investigate the effects of pH on molecules at the water-membrane interface. Here, we compare the performance of enhanced sampling protocols coupled with CpHMD [&hellip;]<\/p>\n","protected":false},"featured_media":0,"template":"","meta":{"msr-url-field":"","msr-podcast-episode":"","msrModifiedDate":"","msrModifiedDateEnabled":false,"ep_exclude_from_search":false,"_classifai_error":"","msr-author-ordering":null,"msr_publishername":"","msr_publisher_other":"","msr_booktitle":"","msr_chapter":"","msr_edition":"","msr_editors":"","msr_how_published":"","msr_isbn":"","msr_issue":"","msr_journal":"","msr_number":"","msr_organization":"","msr_pages_string":"","msr_page_range_start":"","msr_page_range_end":"","msr_series":"","msr_volume":"","msr_copyright":"","msr_conference_name":"","msr_doi":"","msr_arxiv_id":"","msr_s2_paper_id":"","msr_mag_id":"","msr_pubmed_id":"","msr_other_authors":"","msr_other_contributors":"","msr_speaker":"","msr_award":"","msr_affiliation":"","msr_institution":"","msr_host":"","msr_version":"","msr_duration":"","msr_original_fields_of_study":"","msr_release_tracker_id":"","msr_s2_match_type":"","msr_citation_count_updated":"","msr_published_date":"2026-04-12","msr_highlight_text":"","msr_notes":"","msr_longbiography":"","msr_publicationurl":"","msr_external_url":"","msr_secondary_video_url":"","msr_conference_url":"","msr_journal_url":"","msr_s2_pdf_url":"","msr_year":0,"msr_citation_count":0,"msr_influential_citations":0,"msr_reference_count":0,"msr_s2_match_confidence":0,"msr_microsoftintellectualproperty":false,"msr_s2_open_access":false,"msr_s2_author_ids":[],"msr_pub_ids":[{"provider":"s2","id":"3a7bd9b86c39e8966a456900fbb03a312bf6863b"},{"provider":"doi","id":"10.1021\/acs.jpcb.5c07807"}],"msr_hide_image_in_river":null,"footnotes":""},"msr-research-highlight":[],"research-area":[13546,13553],"msr-publication-type":[193715],"msr-publisher":[],"msr-focus-area":[],"msr-locale":[268875],"msr-post-option":[],"msr-field-of-study":[247771],"msr-conference":[],"msr-journal":[270301],"msr-impact-theme":[],"msr-pillar":[],"class_list":["post-1169860","msr-research-item","type-msr-research-item","status-publish","hentry","msr-research-area-computational-sciences-mathematics","msr-research-area-medical-health-genomics","msr-locale-en_us","msr-field-of-study-biomedical-engineering"],"msr_publishername":"","msr_edition":"","msr_affiliation":"","msr_published_date":"2026-04-12","msr_host":"","msr_duration":"","msr_version":"","msr_speaker":"","msr_other_contributors":"","msr_booktitle":"","msr_pages_string":"","msr_chapter":"","msr_isbn":"","msr_journal":"","msr_volume":"","msr_number":"","msr_editors":"","msr_series":"","msr_issue":"","msr_organization":"","msr_how_published":"","msr_notes":"","msr_highlight_text":"","msr_release_tracker_id":"","msr_original_fields_of_study":"","msr_download_urls":"","msr_external_url":"","msr_secondary_video_url":"","msr_longbiography":"","msr_microsoftintellectualproperty":0,"msr_main_download":"","msr_publicationurl":"","msr_doi":"","msr_publication_uploader":[{"type":"doi","viewUrl":"false","id":"false","title":"https:\/\/doi.org\/10.1021\/acs.jpcb.5c07807","label_id":"243106","label":0}],"msr_related_uploader":"","msr_citation_count":0,"msr_citation_count_updated":"","msr_s2_paper_id":"","msr_influential_citations":0,"msr_reference_count":0,"msr_arxiv_id":"","msr_s2_author_ids":[],"msr_s2_open_access":false,"msr_s2_pdf_url":null,"msr_attachments":[],"msr-author-ordering":[{"type":"name","value":"N. 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