Conformational space of flexible biological macromolecules from average data

Bertini, Ivano; Giachetti, Andrea; Luchinat, Claudio; Parigi, Giacomo; Petoukhov, M. V.; Pierattelli, Roberta; Ravera, Enrico; Svergun, D. I.

doi:10.1021/ja1063923

The concept of maximum occurrence (MO), i.e., the maximum percent of time that ﬂexible proteins can spend in any given conformation, is introduced, and a rigorous method is developed to extensively sample the conformational space and to construct MO maps from experimental data. The method is tested in a case study, the ﬂexible two-domain protein calmodulin (CaM), using SAXS and NMR data (i.e., pseudocontact shifts and self-orientation residual dipolar couplings arising from the presence of paramagnetic lanthanide ions), revealing that the “closed” and “fully extended” conformations trapped in the crystalline forms of CaM have MOs of only 5 and 15%, respectively. Compact conformations in general have small MOs, whereas some extended conformations have MO as high as 35%, strongly suggesting these conformations to be most abundant in solution. The method is universally applicable as it requires only standard SAXS data and speciﬁc NMR data on lanthanide derivatives of the protein (using native metal sites or lanthanide tagging). The computer program is publicly available using the grid computing infrastructure through the authors’ Web portal.

Conformational space of flexible biological macromolecules from average data / I.Bertini; A.Giachetti; C.Luchinat; G.Parigi; M.V.Petoukhov; R.Pierattelli; E.Ravera; D.I.Svergun. - In: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. - ISSN 0002-7863. - STAMPA. - 132:(2010), pp. 13553-13558. [10.1021/ja1063923]

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Titolo:	Conformational space of flexible biological macromolecules from average data
Autori di Ateneo:	BERTINI, IVANO GIACHETTI, ANDREA LUCHINAT, CLAUDIO PARIGI, GIACOMO M. V. Petoukhov PIERATTELLI, ROBERTA RAVERA, ENRICO D. I. Svergun mostra contributor esterni nascondi contributor esterni
Autori:	BERTINI, IVANO; GIACHETTI, ANDREA; LUCHINAT, CLAUDIO; PARIGI, GIACOMO; M. V. Petoukhov; PIERATTELLI, ROBERTA; RAVERA, ENRICO; D. I. Svergun
Anno di registrazione:	2010
Rivista:	JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume:	132
Pagina iniziale:	13553
Pagina finale:	13558
Abstract:	The concept of maximum occurrence (MO), i.e., the maximum percent of time that ﬂexible proteins can spend in any given conformation, is introduced, and a rigorous method is developed to extensively sample the conformational space and to construct MO maps from experimental data. The method is tested in a case study, the ﬂexible two-domain protein calmodulin (CaM), using SAXS and NMR data (i.e., pseudocontact shifts and self-orientation residual dipolar couplings arising from the presence of paramagnetic lanthanide ions), revealing that the “closed” and “fully extended” conformations trapped in the crystalline forms of CaM have MOs of only 5 and 15%, respectively. Compact conformations in general have small MOs, whereas some extended conformations have MO as high as 35%, strongly suggesting these conformations to be most abundant in solution. The method is universally applicable as it requires only standard SAXS data and speciﬁc NMR data on lanthanide derivatives of the protein (using native metal sites or lanthanide tagging). The computer program is publicly available using the grid computing infrastructure through the authors’ Web portal.
Handle:	http://hdl.handle.net/2158/394229
Appare nelle tipologie:	1a - Articolo su rivista

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