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Article: Theoretical insight into the photodegradation of a disulfide bridged cyclic tetrapeptide in solution and subsequent fast unfolding-refolding events
Title | Theoretical insight into the photodegradation of a disulfide bridged cyclic tetrapeptide in solution and subsequent fast unfolding-refolding events |
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Authors | |
Issue Date | 2010 |
Publisher | American 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? |
Abstract | We 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 Identifier | http://hdl.handle.net/10722/168450 |
ISSN | 2023 Impact Factor: 2.8 2023 SCImago Journal Rankings: 0.760 |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Chen, X | en_US |
dc.contributor.author | Gao, L | en_US |
dc.contributor.author | Fang, W | en_US |
dc.contributor.author | Phillips, DL | en_US |
dc.date.accessioned | 2012-10-08T03:19:04Z | - |
dc.date.available | 2012-10-08T03:19:04Z | - |
dc.date.issued | 2010 | en_US |
dc.identifier.citation | Journal Of Physical Chemistry B, 2010, v. 114 n. 15, p. 5206-5214 | en_US |
dc.identifier.issn | 1520-6106 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/168450 | - |
dc.description.abstract | We 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.language | eng | en_US |
dc.publisher | American Chemical Society. The Journal's web site is located at http://pubs.acs.org/journal/jpcbfk | en_US |
dc.relation.ispartof | Journal of Physical Chemistry B | en_US |
dc.subject.mesh | Disulfides - Chemistry | en_US |
dc.subject.mesh | Methanol - Chemistry | en_US |
dc.subject.mesh | Molecular Dynamics Simulation | en_US |
dc.subject.mesh | Peptides, Cyclic - Chemistry | en_US |
dc.subject.mesh | Photolysis | en_US |
dc.subject.mesh | Protein Denaturation | en_US |
dc.subject.mesh | Protein Folding | en_US |
dc.subject.mesh | Solutions - Chemistry | en_US |
dc.subject.mesh | Thermodynamics | en_US |
dc.subject.mesh | Ultraviolet Rays | en_US |
dc.title | Theoretical insight into the photodegradation of a disulfide bridged cyclic tetrapeptide in solution and subsequent fast unfolding-refolding events | en_US |
dc.type | Article | en_US |
dc.identifier.email | Phillips, DL:phillips@hku.hk | en_US |
dc.identifier.authority | Phillips, DL=rp00770 | en_US |
dc.description.nature | link_to_subscribed_fulltext | en_US |
dc.identifier.doi | 10.1021/jp1003616 | en_US |
dc.identifier.pmid | 20349927 | - |
dc.identifier.scopus | eid_2-s2.0-77951112593 | en_US |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-77951112593&selection=ref&src=s&origin=recordpage | en_US |
dc.identifier.volume | 114 | en_US |
dc.identifier.issue | 15 | en_US |
dc.identifier.spage | 5206 | en_US |
dc.identifier.epage | 5214 | en_US |
dc.identifier.isi | WOS:000276563000028 | - |
dc.publisher.place | United States | en_US |
dc.identifier.scopusauthorid | Chen, X=9279664000 | en_US |
dc.identifier.scopusauthorid | Gao, L=7401801150 | en_US |
dc.identifier.scopusauthorid | Fang, W=7202236871 | en_US |
dc.identifier.scopusauthorid | Phillips, DL=7404519365 | en_US |
dc.identifier.citeulike | 7023617 | - |
dc.identifier.issnl | 1520-5207 | - |