Abstract
Protein contact networks (PCNs) have been used for the study of protein structure and function for the past decade. In PCNs, each amino acid is considered as a node while the contacts among amino acids are the links/edges. We examined the possible correlation between the closeness centrality measure of amino acids within PCNs and their mobility as known from NMR spin relaxation experiments and molecular dynamic (MD) simulations. The pivotal observation was that plasticity within a protein stretch correlated inversely to closeness centrality. Effects on protein conformational plasticity caused by the formation of disulfide bonds or protein–protein interactions were also identified by the PCN analysis measure closeness centrality and the hereby introduced percentage of closeness centrality perturbation (% CCP). All the comparisons between PCN measures, NMR data, and MDs were performed in a set of proteins of different biological functions and structures: the core protease domain of anthrax lethal factor, the N-terminal RING domain of E3 Ub ligase Arkadia, the reduced and oxidized forms of human thioredoxin 1, and the ubiquitin molecules (Ub) of the catalytic Ub–RING–E3–E2–Ub complex of E3 ligase Ark2.The graph theory analysis of PCNs could thus provide a general method for assessing the conformational dynamics of free proteins and putative plasticity changes between different protein forms (apo/complexed or reduced/oxidized).
Highlights
Proteins are largely dynamic molecules with their overall conformation affecting their biological function
NMR experiments based on the methyl-TROSY effect that significantly improves spectral resolution and sensitivity have been used for the study of protein conformation of supramolecular complexes with molecular masses extending to 1 MDa [3]
Methods that probe into the protein dynamics of these undefined parts are largely computational and may (i) use automated protocols for the identification of functional dynamics from X-ray structures [4]; (ii) classify proteins according to their mobility patterns, improving annotation of protein function on the basis of protein dynamics [5]; 4.0/)
Summary
Proteins are largely dynamic molecules with their overall conformation affecting their biological function. Crystallographic B-factors, NMR spin relaxation measurements, and molecular dynamic (MD) simulations provide insights into protein flexibility on an atomic scale. NMR spin relaxation experiments provide site-specific information about backbone and sidechain dynamics throughout the protein. NMR experiments based on the methyl-TROSY effect that significantly improves spectral resolution and sensitivity have been used for the study of protein conformation of supramolecular complexes with molecular masses extending to 1 MDa [3]. Protein parts of increased flexibility will not diffract long enough and may not be visible in crystal structures. Methods that probe into the protein dynamics of these undefined parts are largely computational and may (i) use automated protocols for the identification of functional dynamics from X-ray structures [4]; (ii) classify proteins according to their mobility patterns, improving annotation of protein function on the basis of protein dynamics [5]; 4.0/)
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