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Article: Theoretical insight into the photodegradation of a disulfide bridged cyclic tetrapeptide in solution and subsequent fast unfolding-refolding events

TitleTheoretical insight into the photodegradation of a disulfide bridged cyclic tetrapeptide in solution and subsequent fast unfolding-refolding events
Authors
Issue Date2010
PublisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/journal/jpcbfk
Citation
Journal Of Physical Chemistry B, 2010, v. 114 n. 15, p. 5206-5214 How to Cite?
AbstractWe report the photoinduced peptide bond (C-N) of an amide unit and S-S bond fission mechanisms of the cyclic tetrapeptide [cyclo(Boc-Cys-Pro-Aib-Cys-OMe)] in methanol solvent by using high-level CASSCF/CASPT2/Amber quantum mechanical/molecular mechanical (QM/MM) calculations. The subsequent energy transport and unfolding-refolding events are characterized by using a semiempirical QM/MM molecular dynamics (MD) simulation methodology that is developed in the present work. In the case of high-energy excitation with <193 nm light, the tetrapeptide molecule in the 1nπ* surface overcomes two barriers with ∼10.0 kcal/mol, respectively, and uses energy consumption for breaking the hydrogen bond as well as the N-C bond in the amide unit, ultimately leading to the ground state via a conical intersection of CI (S NP/S 0) by structural changes of an increased N-C distance and a O-C-C angle in the amide unit (a two-dimensional model of the reaction coordinates). Following this point, relaxation to a hot molecule with its original structure in the ground state is the predominant decay channel. A large amount of heat (∼110.0 kcal/mol) is initially accumulated in the region of the targeted point of the photoexcitation, and more than 60% of the heat is rapidly dissipated into the solvent on the femtosecond time scale. The relatively slower propagation of heat along the peptide backbone reaches a phase of equilibration within 3 ps. A 300 nm photon of light initiates the relaxation along the repulsive S σσ( 1σσ) state and this decays to the CI (S σσ/S 0) in concomitance with the separation of the disulfide bond. Once cysteinyl radicals are generated, the polar solvent of methanol molecules rapidly diffuses around the radicals, forming a solvent cage and reducing the possibility of close contact in a physical sense. The fast unfolding-refolding event is triggered by S-S bond fission and powered by dramatic thermal motion of the methanol solvent that benefits from heat dissipation. The β-turn opening (unfolding) can be achieved in about 120 ps without the inclusion of the time associated with the photochemical steps and eventually relaxes to a 3 10-helix structural architecture (refolding) within 200 ps. © 2010 American Chemical Society.
Persistent Identifierhttp://hdl.handle.net/10722/168450
ISSN
2015 Impact Factor: 3.187
2015 SCImago Journal Rankings: 1.414
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChen, Xen_US
dc.contributor.authorGao, Len_US
dc.contributor.authorFang, Wen_US
dc.contributor.authorPhillips, DLen_US
dc.date.accessioned2012-10-08T03:19:04Z-
dc.date.available2012-10-08T03:19:04Z-
dc.date.issued2010en_US
dc.identifier.citationJournal Of Physical Chemistry B, 2010, v. 114 n. 15, p. 5206-5214en_US
dc.identifier.issn1520-6106en_US
dc.identifier.urihttp://hdl.handle.net/10722/168450-
dc.description.abstractWe report the photoinduced peptide bond (C-N) of an amide unit and S-S bond fission mechanisms of the cyclic tetrapeptide [cyclo(Boc-Cys-Pro-Aib-Cys-OMe)] in methanol solvent by using high-level CASSCF/CASPT2/Amber quantum mechanical/molecular mechanical (QM/MM) calculations. The subsequent energy transport and unfolding-refolding events are characterized by using a semiempirical QM/MM molecular dynamics (MD) simulation methodology that is developed in the present work. In the case of high-energy excitation with <193 nm light, the tetrapeptide molecule in the 1nπ* surface overcomes two barriers with ∼10.0 kcal/mol, respectively, and uses energy consumption for breaking the hydrogen bond as well as the N-C bond in the amide unit, ultimately leading to the ground state via a conical intersection of CI (S NP/S 0) by structural changes of an increased N-C distance and a O-C-C angle in the amide unit (a two-dimensional model of the reaction coordinates). Following this point, relaxation to a hot molecule with its original structure in the ground state is the predominant decay channel. A large amount of heat (∼110.0 kcal/mol) is initially accumulated in the region of the targeted point of the photoexcitation, and more than 60% of the heat is rapidly dissipated into the solvent on the femtosecond time scale. The relatively slower propagation of heat along the peptide backbone reaches a phase of equilibration within 3 ps. A 300 nm photon of light initiates the relaxation along the repulsive S σσ( 1σσ) state and this decays to the CI (S σσ/S 0) in concomitance with the separation of the disulfide bond. Once cysteinyl radicals are generated, the polar solvent of methanol molecules rapidly diffuses around the radicals, forming a solvent cage and reducing the possibility of close contact in a physical sense. The fast unfolding-refolding event is triggered by S-S bond fission and powered by dramatic thermal motion of the methanol solvent that benefits from heat dissipation. The β-turn opening (unfolding) can be achieved in about 120 ps without the inclusion of the time associated with the photochemical steps and eventually relaxes to a 3 10-helix structural architecture (refolding) within 200 ps. © 2010 American Chemical Society.en_US
dc.languageengen_US
dc.publisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/journal/jpcbfken_US
dc.relation.ispartofJournal of Physical Chemistry Ben_US
dc.subject.meshDisulfides - Chemistryen_US
dc.subject.meshMethanol - Chemistryen_US
dc.subject.meshMolecular Dynamics Simulationen_US
dc.subject.meshPeptides, Cyclic - Chemistryen_US
dc.subject.meshPhotolysisen_US
dc.subject.meshProtein Denaturationen_US
dc.subject.meshProtein Foldingen_US
dc.subject.meshSolutions - Chemistryen_US
dc.subject.meshThermodynamicsen_US
dc.subject.meshUltraviolet Raysen_US
dc.titleTheoretical insight into the photodegradation of a disulfide bridged cyclic tetrapeptide in solution and subsequent fast unfolding-refolding eventsen_US
dc.typeArticleen_US
dc.identifier.emailPhillips, DL:phillips@hku.hken_US
dc.identifier.authorityPhillips, DL=rp00770en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1021/jp1003616en_US
dc.identifier.pmid20349927-
dc.identifier.scopuseid_2-s2.0-77951112593en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77951112593&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume114en_US
dc.identifier.issue15en_US
dc.identifier.spage5206en_US
dc.identifier.epage5214en_US
dc.identifier.isiWOS:000276563000028-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridChen, X=9279664000en_US
dc.identifier.scopusauthoridGao, L=7401801150en_US
dc.identifier.scopusauthoridFang, W=7202236871en_US
dc.identifier.scopusauthoridPhillips, DL=7404519365en_US
dc.identifier.citeulike7023617-

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