dc.contributor.author | Formoso Estensoro, Elena | |
dc.contributor.author | Limongelli, Vittorio | |
dc.contributor.author | Parrinello, Michele | |
dc.date.accessioned | 2016-05-05T13:21:06Z | |
dc.date.available | 2016-05-05T13:21:06Z | |
dc.date.issued | 2015-02-12 | |
dc.identifier.citation | Scientific Reports 5 : (2015) // Article ID 8425 | es |
dc.identifier.issn | 2045-2322 | |
dc.identifier.uri | http://hdl.handle.net/10810/18166 | |
dc.description.abstract | Adenylate Kinase (AK) is a signal transducing protein that regulates cellular energy homeostasis balancing between different conformations. An alteration of its activity can lead to severe pathologies such as heart failure, cancer and neurodegenerative diseases. A comprehensive elucidation of the large-scale conformational motions that rule the functional mechanism of this enzyme is of great value to guide rationally the development of new medications. Here using a metadynamics-based computational protocol we elucidate the thermodynamics and structural properties underlying the AK functional transitions. The free energy estimation of the conformational motions of the enzyme allows characterizing the sequence of events that regulate its action. We reveal the atomistic details of the most relevant enzyme states, identifying residues such as Arg119 and Lys13, which play a key role during the conformational transitions and represent druggable spots to design enzyme inhibitors. Our study offers tools that open new areas of investigation on large-scale motion in proteins. | es |
dc.description.sponsorship | This work was supported by grants from the Swiss National Supercomputing Centre - CSCS under project s358 and Italian MIUR-PRIN 2010/2011 (E61J12000210001). | es |
dc.language.iso | eng | es |
dc.publisher | Nature Publishing | es |
dc.rights | info:eu-repo/semantics/openAccess | es |
dc.subject | particle mesh ewald | es |
dc.subject | molecular-dynamics | es |
dc.subject | scherichia-coli | es |
dc.subject | free-energy | es |
dc.subject | conformational transitions | es |
dc.subject | substrate-binding | es |
dc.subject | ligand-binding | es |
dc.subject | mechanism | es |
dc.subject | proteins | es |
dc.subject | simulation | es |
dc.title | Energetics and Structural Characterization of the large-scale Functional Motion of Adenylate Kinase | es |
dc.type | info:eu-repo/semantics/article | es |
dc.rights.holder | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ | es |
dc.relation.publisherversion | http://www.nature.com/articles/srep08425 | es |
dc.identifier.doi | 10.1038/srep08425 | |
dc.departamentoes | Ciencia y tecnología de polímeros | es_ES |
dc.departamentoeu | Polimeroen zientzia eta teknologia | es_ES |
dc.subject.categoria | MULTIDISCIPLINARY SCIENCES | |