Using molecular principal axes for structural comparison: determining the tertiary changes of a FAB antibody domain induced by antigenic binding

Silverman, B. David
January 2007
BMC Structural Biology;2007, Vol. 7, p77
Academic Journal
Background: Comparison of different protein x-ray structures has previously been made in a number of different ways; for example, by visual examination, by differences in the locations of secondary structures, by explicit superposition of structural elements, e.g. α-carbon atom locations, or by procedures that utilize a common symmetry element or geometrical feature of the structures to be compared. Results: A new approach is applied to determine the structural changes that an antibody protein domain experiences upon its interaction with an antigenic target. These changes are determined with the use of two different, however comparable, sets of principal axes that are obtained by diagonalizing the second-order tensors that yield the moments-of-geometry as well as an ellipsoidal characterization of domain shape, prior to and after interaction. Determination of these sets of axes for structural comparison requires no internal symmetry features of the domains, depending solely upon their representation in three-dimensional space. This representation may involve atomic, Cα, or residue centroid coordinates. The present analysis utilizes residue centroids. When the structural changes are minimal, the principal axes of the domains, prior to and after interaction, are essentially comparable and consequently may be used for structural comparison. When the differences of the axes cannot be neglected, but are nevertheless slight, a smaller relatively invariant substructure of the domains may be utilized for comparison. The procedure yields two distance metrics for structural comparison. First, the displacements of the residue centroids due to antigenic binding, referenced to the ellipsoidal principal axes, are noted. Second, changes in the ellipsoidal distances with respect to the non-interacting structure provide a direct measure of the spatial displacements of the residue centroids, towards either the interior or exterior of the domain. Conclusion: With use of x-ray data from the protein data bank (PDB), these two metrics are shown to highlight, in a manner different from before, the structural changes that are induced in the overall domains as well as in the H3 loops of the complementarity-determining regions (CDR) upon FAB antibody binding to a truncated and to a synthetic hemagglutinin viral antigenic target.


Related Articles

  • B K-Edge XANES of Superstructural Units in Borate Glasses. Sˇipr, O.; Sˇimunek, A.; Rocca, F. // AIP Conference Proceedings;2007, Vol. 882 Issue 1, p446 

    The potential of x-ray absorption near-edge structure (XANES) spectroscopy for studying medium range order in borate glasses is assessed by theoretical modelling of the spectra. B K edge XANES is calculated in case that B atoms are located in isolated BO3 and BO4 units and in case that B atom...

  • On the spectral frequency distribution of translational vibrations in a face-centered cubic lattice of the C60 fullerite. Mikhal'chenko, V. P.; Motskin, V. V. // Physics of the Solid State;Jul2006, Vol. 48 Issue 7, p1398 

    The spectral frequency distribution g(ω) of translational lattice vibrations in the face-centered cubic phase of the C60 fullerite at T = 300 K is calculated by the superposition method. The contribution from the translational vibrations to the heat capacity C V of the C60 fullerite and the...

  • Systematic study of basis set superposition errors in the calculated interaction energy of two HF molecules. Schwenke, David W.; Truhlar, Donald G. // Journal of Chemical Physics;3/1/1985, Vol. 82 Issue 5, p2418 

    We have calculated the interaction energy of two HF molecules at the single-configuration Hartree–Fock level using 34 different basis sets in an effort to assess the reliability and usefulness of the counterpoise correction to account for basis set incompleteness. We find large...

  • Bimolecular annihilation reactions with immobile reactants. Schnörer, H.; Kuzovkov, V.; Blumen, A. // Journal of Chemical Physics;2/15/1990, Vol. 92 Issue 4, p2310 

    We study the bimolecular annihilation reaction A+B→0 with immobile reactants in arbitrary dimension. For this we derive a closed set of integrodifferential equations by using Kirkwood’s superposition approximation to decouple the infinite hierarchy of equations for the many-center...

  • Application of the superposition model to calculate the zero-field splittings in molecules. Weltner, W.; Van Zee, R. J. // Journal of Chemical Physics;5/15/1985, Vol. 82 Issue 10, p4492 

    b02 =D zero-field splitting parameters are calculated for the GdF3 and MnX2 (X=F, Cl, Br) molecules using the superposition model with intrinsic parameters obtained from crystal measurements and interatomic distances from gas-phase electron diffraction, where available.

  • Computational Study of Supramolecular Bis-porphyrin “Molecular Tweezers”. Margetić, Davor; Warrener, Ronald N.; Butler, Doug N.; Officer, David // Theoretical Chemistry Accounts: Theory, Computation, & Modeling;Mar2007, Vol. 117 Issue 2, p239 

    A computational study of a series of space separated bis-porphyrin “molecular tweezers” using semiempirical (AM1) and DFT (B3LYP and PBE1PBE) methods has been carried out. It was found that polynorbornane bis-porphyrin systems are significantly less rigid than previously thought. The...

  • Biological chemistry: Catalytic competition for cells. Cornish, Virginia W. // Nature;3/9/2006, Vol. 440 Issue 7081, p156 

    The article reports on a study about catalytic competition for cells. Researchers found that water-in-oil-in-water emulsions of the cell's machinery allow fluorescence activated cell sorting of individual droplets containing not only a protein and its unique DNA sequence, but also fluorogenic...

  • Conformational Features and Geometry of Molecules in Crystals of Bridging ortho,ortho-Bisphenols and Related Compounds: A Review. Chetkina, L. A.; Belsky, V. K. // Crystallography Reports;Jul2005, Vol. 50 Issue 4, p571 

    This paper generalizes and systematizes the main results of X-ray structure investigations of bridging ortho,ortho-bisphenols and related compounds. The conformational characteristics and geometric parameters of molecules and hydrogen bonds in ortho,ortho-methylene-bisphenols, their derivatives,...

  • Theory of interaction between helical molecules. Kornyshev, A.A.; Leikin, S. // Journal of Chemical Physics;9/1/1997, Vol. 107 Issue 9, p3656 

    Explains the theory of interaction between helical molecules. Interaction between cylindrical molecules with an arbitrary distribution of discrete surface charges; Interaction between molecules with helical symmetry.


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics