| Title | Trans-cis Switching Mechanisms in Proline Analogues and Their Relevance for the Gating of the 5-HT(3) Receptor. | | Author(s) | Melis C, Bussi G, Lummis SC, Molteni C | | Institution | Physics Department, King's College London, Strand, London, WC2R 2LS U.K., Dipartimento di Fisica, Universita di Modena e Reggio Emilia, and CNR-INFM Center on nanoStructures and bioSystems at Surfaces (S3), Via Campi 213/A, I-41100 Modena, Italy, Department of Chemistry and Applied Biosciences, ETH Zurich c/o USI-Campus, via Buffi 13, CH-6900 Lugano, Switzerland, Biochemistry Department, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, U.K. | | Source | J Phys Chem B 2009 Aug 10. | | Abstract | Trans-cis isomerization of a proline peptide bond is a potential mechanism to open the channel of the 5-HT(3) receptor. Here, we have used the metadynamics method to theoretically explore such a mechanism. We have determined the free energy surfaces in aqueous solution of a series of dipeptides of proline analogues and evaluated the free energy difference between the cis and trans isomers. These theoretical results were then compared with data from mutagenesis experiments, in which the response of the 5-HT(3) receptor was measured when the proline at the apex of the M2-M3 transmembrane domain loop was mutated. The strong correlation between the experimental and the theoretical data supports the existence of a trans-cis proline switch for opening the 5-HT(3) receptor ion channel. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19663504 |
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