Molecular dynamics study of naturally existing cavity couplings in proteins
Barbany, Montserrat (Institut de Recerca Biomèdica de Lleida)
Meyer, Tim (Max-Planck-Institut für biophysikalische Chemie)
Hospital, Adam (Institut de Recerca Biomèdica)
Faustino, Ignacio (Institut de Recerca Biomèdica)
D'Abramo, Marco (Università degli Studi di Roma "La Sapienza". Dipartimento di Chimica)
Morata, Jordi (Centre de Recerca en Agrigenòmica)
Orozco López, Modesto (Institut de Recerca Biomèdica)
de la Cruz, Xavier (Institució Catalana de Recerca i Estudis Avançats)

Data:	2015
Resum:	Couplings between protein sub-structures are a common property of protein dynamics. Some of these couplings are especially interesting since they relate to function and its regulation. In this article we have studied the case of cavity couplings because cavities can host functional sites, allosteric sites, and are the locus of interactions with the cell milieu. We have divided this problem into two parts. In the first part, we have explored the presence of cavity couplings in the natural dynamics of 75 proteins, using 20 ns molecular dynamics simulations. For each of these proteins, we have obtained two trajectories around their native state. After applying a stringent filtering procedure, we found significant cavity correlations in 60% of the proteins. We analyze and discuss the structure origins of these correlations, including neighbourhood, cavity distance, etc. In the second part of our study, we have used longer simulations (≥100ns) from the MoDEL project, to obtain a broader view of cavity couplings, particularly about their dependence on time. Using moving window computations we explored the fluctuations of cavity couplings along time, finding that these couplings could fluctuate substantially during the trajectory, reaching in several cases correlations above 0. 25/0. 5. In summary, we describe the structural origin and the variations with time of cavity couplings. We complete our work with a brief discussion of the biological implications of these results.
Ajuts:	European Commission 261523 Ministerio de Economía y Competitividad BIO2012/40133 Ministerio de Economía y Competitividad BIO2012/32868 Ministerio de Ciencia e Innovación BCV-2009-1-0003 Ministerio de Ciencia e Innovación BFU2009/11527 Ministerio de Ciencia e Innovación BCV-2008-1-0012 Ministerio de Ciencia e Innovación 200420E578
Nota:	Altres ajuts: MSC/CD08/00241
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	BMC genomics, Vol. 10, issue 3 (March 2015) , e0119978, ISSN 1471-2164

DOI: 10.1371/journal.pone.0119978
PMID: 25816327

28 p, 1.7 MB

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