Optimal contact map alignment of protein–protein interfaces

The long-standing problem of constructing protein structure alignments is of central importance in computational biology. The main goal is to provide an alignment of residue correspondences, in order to identify homologous residues across chains. A critical next step of this is the alignment of protein complexes and their interfaces. Here, we introduce the program CMAPi, a two-dimensional dynamic programming algorithm that, given a pair of protein complexes, optimally aligns the contact maps of their interfaces: it produces polynomial-time near-optimal alignments in the case of multiple complexes. We demonstrate the efficacy of our algorithm on complexes from PPI families listed in the SCOPPI database and from highly divergent cytokine families. In comparison to existing techniques, CMAPi generates more accurate alignments of interacting residues within families of interacting proteins, especially for sequences with low similarity. While previous methods that use an all-atom based representation of the interface have been successful, CMAPi's use of a contact map representation allows it to be more tolerant to conformational changes and thus to align more of the interaction surface. These improved interface alignments should enhance homology modeling and threading methods for predicting PPIs by providing a basis for generating template profiles for sequence–structure alignment

D-state configurations in the electromagnetic form factors of the nucleon and the Delta(1232) resonance

The $\Delta-N$ electromagnetic transition form factors are calculated in the Poincar\'e covariant quark model in three forms of relativistic kinematics. Addition of $D-$state components to pure $S-$state model wave functions, chosen so as to reproduce the empirical elastic electromagnetic nucleon form factors with single constituent currents, brings the calculated $R_{EM}$ ratio for the $\Delta(1232)\to N\gamma$ transition closer to the empirical values in instant and point form kinematics. The calculated $R_{SM}$ ratio is insensitive to the $D-$state component. In front form kinematics the substantial violation of the angular condition for the spin 3/2 resonance transition amplitude in the impulse approximation prevents a unique determination of $R_{EM}$ and $R_{SM}$, both of which are very sensitive to $D-$state components. In no form of kinematics do $D-$state deformations of the rest frame baryon wave functions alone suffice for a description of the empirical values of these ratios.Comment: 11 figures, elsevier forma

Baryon Current Matrix Elements in a Light-Front Framework

Current matrix elements and observables for electro- and photo-excitation of baryons from the nucleon are studied in a light-front framework. Relativistic effects are estimated by comparison to a nonrelativistic model, where we use simple basis states to represent the baryon wavefunctions. Sizeable relativistic effects are found for certain transitions, for example, to radial excitations such as that conventionally used to describe to the Roper resonance. A systematic study shows that the violation of rotational covariance of the baryon transition matrix elements stemming from the use of one-body currents is generally small.Comment: 32 pages, LaTeX, 10 postscript figures, uses epsf.sty; figures uuencoded with uufiles (or available by request in .ps or hardcopy form

Crystal structure of the anthrax lethal factor

Lethal factor (LF) is a protein (relative molecular mass 90,000) that is critical in the pathogenesis of anthrax(1-3). It is a highly specific protease that cleaves members of the mitogen-activated protein kinase kinase (MAPKK) family near to their amino termini, leading to the inhibition of one or more signalling pathways(4-6). Here we describe the crystal structure of LF and its complex with the N terminus of MAPKK-2. LF comprises four domains: domain I binds the membrane-translocating component of anthrax toxin, the protective antigen (PA); domains II, III and IV together create a long deep groove that holds the 16-residue N-terminal tail of MAPKK-2 before cleavage. Domain II resembles the ADP-ribosylating toxin from Bacillus cereus, but the active site has been mutated and recruited to augment substrate recognition. Domain III is inserted into domain II, and seems to have arisen from a repeated duplication of a structural element of domain II. Domain IV is distantly related to the zinc metalloprotease family, and contains the catalytic centre; it also resembles domain I. The structure thus reveals a protein that has evolved through a process of gene duplication, mutation and fusion, into an enzyme with high and unusual specificity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62772/1/414229a0.pd

Space-Time Supersymmetry of Extended Fermionic Strings in 2+22 + 2 Dimensions

The $N=2$ fermionic string theory is revisited in light of its recently proposed equivalence to the non-compact $N=4$ fermionic string model. The issues of space-time Lorentz covariance and supersymmetry for the BRST quantized $N=2$ strings living in uncompactified $2 + 2$ dimensions are discussed. The equivalent local quantum supersymmetric field theory appears to be the most transparent way to represent the space-time symmetries of the extended fermionic strings and their interactions. Our considerations support the Siegel's ideas about the presence of $SO(2,2)$ Lorentz symmetry as well as at least one self-dual space-time supersymmetry in the theory of the $N=2(4)$ fermionic strings, though we do not have a compelling reason to argue about the necessity of the {\it maximal} space-time supersymmetry. The world-sheet arguments about the absence of all string massive modes in the physical spectrum, and the vanishing of all string-loop amplitudes in the Polyakov approach, are given on the basis of general consistency of the theory.Comment: 29 pages, LaTeX, ITP-UH-1/9

Twisting the N=2 String

The most general homogeneous monodromy conditions in $N{=}2$ string theory are classified in terms of the conjugacy classes of the global symmetry group $U(1,1)\otimes{\bf Z}_2$. For classes which generate a discrete subgroup \G, the corresponding target space backgrounds {\bf C}^{1,1}/\G include half spaces, complex orbifolds and tori. We propose a generalization of the intercept formula to matrix-valued twists, but find massless physical states only for $\Gamma{=}{\bf 1}$ (untwisted) and $\Gamma{=}{\bf Z}_2$ (\`a la Mathur and Mukhi), as well as for $\Gamma$ being a parabolic element of $U(1,1)$. In particular, the sixteen ${\bf Z}_2$-twisted sectors of the $N{=}2$ string are investigated, and the corresponding ground states are identified via bosonization and BRST cohomology. We find enough room for an extended multiplet of `spacetime' supersymmetry, with the number of supersymmetries being dependent on global `spacetime' topology. However, world-sheet locality for the chiral vertex operators does not permit interactions among all massless `spacetime' fermions.Comment: 42 pages, LaTeX, no figures, 120 kb, ITP-UH-24/93, DESY 93-191 (abstract and introduction clarified, minor corrections added

Activation measurements in support of the 14 MeV neutron calibration of JET neutron monitors

In preparation for the upcoming deuterium-tritium campaign at the JET tokamak, the ex-vessel fission chamber neutron diagnostics and the neutron activation system will be calibrated in absolute terms at 14 MeV neutron energy, to a required accuracy of less than 10%. Two nominally identical DT neutron generators were chosen as the calibration sources, both of which were fully calibrated and characterized at the UK's National Physical Laboratory. The neutron activation method was adopted as a complementary method for the purpose of determining the absolute value of the neutron yield from the neutron generators and to provide a means of cross check for the active detection methods being employed. The work being presented here shows the derivation of the neutron emission rate from the neutron generators based upon experimental activation foil measurements

Knowledge-based energy functions for computational studies of proteins

This chapter discusses theoretical framework and methods for developing knowledge-based potential functions essential for protein structure prediction, protein-protein interaction, and protein sequence design. We discuss in some details about the Miyazawa-Jernigan contact statistical potential, distance-dependent statistical potentials, as well as geometric statistical potentials. We also describe a geometric model for developing both linear and non-linear potential functions by optimization. Applications of knowledge-based potential functions in protein-decoy discrimination, in protein-protein interactions, and in protein design are then described. Several issues of knowledge-based potential functions are finally discussed.Comment: 57 pages, 6 figures. To be published in a book by Springe