Dynamic properties of oligomers that characterize low-frequency normal modes

Abstract

Dynamics of oligomeric proteins (one trimer, two tetramers, and one hexamer) were studied by elastic network model-based normal mode analysis to characterize their large-scale concerted motions. First, the oligomer motions were simplified by considering rigid-body motions of individual subunits. The subunit motions were resolved into three components in a cylindrical coordinate system: radial, tangential, and axial ones. Single component is dominant in certain normal modes. However, more than one component is mixed in others. The subunits move symmetrically in certain normal modes and as a standing wave with several wave nodes in others. Secondly, special attention was paid to atoms on inter-subunit interfaces. Their displacement vectors were decomposed into intrasubunit deformative (internal) and rigid-body (external) motions in individual subunits. The fact that most of the cosines of the internal and external motion vectors were negative for the atoms on the inter-subunit interfaces, indicated their opposing movements. Finally, a structural network of residues defined for each normal mode was investigated; the network was constructed by connecting two residues in contact and moving coherently. The centrality measure "betweenness" of each residue was calculated for the networks. Several residues with significantly high betweenness were observed on the inter-subunit interfaces. The results indicate that these residues are responsible for oligomer dynamics. It was also observed that amino acid residues with significantly high betweenness were more conservative. This supports that the betweenness is an effective characteristic for identifying an important residue in protein dynamics.Key words: betweenness, degeneracy of normal modes, conservation of amino acid residues, protein structure network, cylindrical coordinate system Most proteins function in an oligomeric form [1]. An advantage of oligomers over monomers is that the oligomeric form permits proteins to initiate allostery and cooperativity in achieving their function. Studies on the dynamics of oligomers can provide key information that reveals the mechanism of the allostery and cooperativity. Molecular dynamics (MD) simulation and normal mode analysis (NMA) can be effective theoretical methods to address this problem [2-9]. Although they can generate a large amount of data regarding protein motions at the atomic level and the motions Dynamics of oligomeric proteins were studied by elastic network model-based normal mode analysis to characterize their large-scale concerted motions. (1) The rigid-body motions of individual subunits were characterized by the radial, tangential, and axial components in a cylindrical coordinate system. (2) The motions of atoms on the intersubunit interfaces were characterized by the opposing motions of intra-subunit deformation and rigid-body motion of the subunit. (3) A dynamic protein structure network was defined in each mode, and the centrality measure, betweenness, was calculated for each residue. The results indicate tha...

Insight into Shared Properties and Differential Dynamics and Specificity of Secretory Phospholipase A2 Family Members

“…The low mobility of conserved residues and high mobility of variable residues are consistent with the concept of coupling among sequence, structure, and dynamics variations, which has been validated in several earlier studies. 51,52 Such juxtaposition of sequentially conserved (dynamically constrained) and sequentially variable (dynamically flexible) residues appears to be a design feature to mutually support the respective generic and specific properties of sPLA 2 family members.…”

Protein conformational switch discerned via network centrality properties

“…At times, a specific measurement was used in an application to specific PSNs and no rationale on choosing a measurement or comparison between measurements was given. Nevertheless, residues with high BC values have been identified in important biological roles such as the inter-subunit interfaces of oligomeric proteins [31] , the stability of the enzymatic core of c-Abl and c-Src kinases [32] , and the conserved (predominantly hydrophobic) residues of cyclophilin A [33] . Furthermore, two studies (using 178 and 283 structures respectively) found that catalytic sites have significantly higher CC values [34] , [35] .…”