title: Dynamics and energetics: a consensus analysis of the impact of calcium on EF-CaM protein complex.
abstract: We have studied the relationship between dynamical correlations and energetic contributions in an attempt to model the transmission of information inside protein-protein complexes. The complex formed between the edema factor (EF) of Bacillus anthracis and calmodulin (CaM) was taken as an example, as the formation and stability of the complex depend on the calcium complexation level. The effect of calcium through EF-CaM residue network has been investigated with various approaches: 1), the elastic network model; 2), the local feature analysis; 3), the generalized correlations; and 4), the energetic dependency maps (EDMs), on 15-ns molecular dynamics simulations of the complex loaded with 0, 2, or 4 Ca2+ ions. The elastic network model correctly describes the basic architecture of the complex but is poorly sensitive to the level of calcium compared to the other methods. The local feature analysis allows us to characterize the local dynamics of the complex and the propagation of the calcium signal through CaM. The analyses of global dynamics and energetics--through generalized correlations and EDMs--provide a comprehensive picture of EF-CaM architecture and can be unified by using the concept of residue network connectedness. A medium connectedness, defined as the ability of each residue to communicate with all remaining parts of the complex, is observed for the 2Ca2+ level, which was experimentally identified as the most stable form of EF-CaM. The hierarchy of relative stabilities given by the EDMs sheds a new light on the EF-CaM interaction mechanism described experimentally and supports an organization of the complex architecture centered around nucleation points.
authors.affiliation: Unité de Bioinformatique Structurale, CNRS URA 2185, Département de Biologie, Structurale et Chimie, Institut Pasteur, Paris, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Laine
authors.forename: Arnaud
authors.initials: A
authors.lastname: Blondel
authors.forename: Thérèse E
authors.initials: TE
authors.lastname: Malliavin
mesh_terms: D000942:Antigens, Bacterial / Q000737:chemistry*; D001427:Bacterial Toxins / Q000737:chemistry*; D002118:Calcium / Q000737:chemistry*; D002147:Calmodulin / Q000737:chemistry*; D016000:Cluster Analysis; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D008956:Models, Chemical; D008958:Models, Molecular; D020836:Protein Structure, Quaternary; D013816:Thermodynamics
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D002147:Calmodulin; C030325:anthrax toxin; D002118:Calcium