Three-dimensional Structure Databases of Biological Macromolecules

Databases of three-dimensional structures of proteins (and their associated molecules) provide: (a)Curated repositories of coordinates of experimentally determined structures, including extensive metadata; for instance information about provenance, details about data collection and interpretation, and validation of results.(b)Information-retrieval tools to allow searching to identify entries of interest and provide access to them.(c)Links among databases, especially to databases of amino-acid and genetic sequences, and of protein function; and links to software for analysis of amino-acid sequence and protein structure, and for structure prediction.(d)Collections of predicted three-dimensional structures of proteins. These will become more and more important after the breakthrough in structure prediction achieved by AlphaFold2. The single global archive of experimentally determined biomacromolecular structures is the Protein Data Bank (PDB). It is managed by wwPDB, a consortium of five partner institutions: the Protein Data Bank in Europe (PDBe), the Research Collaboratory for Structural Bioinformatics (RCSB), the Protein Data Bank Japan (PDBj), the BioMagResBank (BMRB), and the Electron Microscopy Data Bank (EMDB). In addition to jointly managing the PDB repository, the individual wwPDB partners offer many tools for analysis of protein and nucleic acid structures and their complexes, including providing computer-graphic representations. Their collective and individual websites serve as hubs of the community of structural biologists, offering newsletters, reports from Task Forces, training courses, and “helpdesks,” as well as links to external software. Many specialized projects are based on the information contained in the PDB. Especially important are SCOP, CATH, and ECOD, which present classifications of protein domains

The eta' meson from lattice QCD

We study the flavour singlet pseudoscalar mesons from first principles using lattice QCD. With N_f=2 flavours of light quark, this is the so-called eta_2 meson and we discuss the phenomenological status of this. Using maximally twisted-mass lattice QCD, we extract the mass of the eta_2 meson at two values of the lattice spacing for lighter quarks than previously discussed in the literature. We are able to estimate the mass value in the limit of light quarks with their physical masses.Comment: 16 pages: version accepted for publicatio

Introduction to protein folding for physicists

The prediction of the three-dimensional native structure of proteins from the knowledge of their amino acid sequence, known as the protein folding problem, is one of the most important yet unsolved issues of modern science. Since the conformational behaviour of flexible molecules is nothing more than a complex physical problem, increasingly more physicists are moving into the study of protein systems, bringing with them powerful mathematical and computational tools, as well as the sharp intuition and deep images inherent to the physics discipline. This work attempts to facilitate the first steps of such a transition. In order to achieve this goal, we provide an exhaustive account of the reasons underlying the protein folding problem enormous relevance and summarize the present-day status of the methods aimed to solving it. We also provide an introduction to the particular structure of these biological heteropolymers, and we physically define the problem stating the assumptions behind this (commonly implicit) definition. Finally, we review the 'special flavor' of statistical mechanics that is typically used to study the astronomically large phase spaces of macromolecules. Throughout the whole work, much material that is found scattered in the literature has been put together here to improve comprehension and to serve as a handy reference.Comment: 53 pages, 18 figures, the figures are at a low resolution due to arXiv restrictions, for high-res figures, go to http://www.pabloechenique.co

Improved B -> pi l nu_l form factors from the lattice

We present the results of a lattice computation of the form factors for B^0 ->pi^- l^+nu_l decays near zero-recoil. These results will allow a determination of the CKM matrix element |Vub| when measurements of the differential decay rate become available. We also provide models for extrapolation of the form factors and rate to the full recoil range. Our computation is performed in the quenched approximation to QCD on a 24^3x48 lattice at beta=6.2, using a non-perturbatively O(a)-improved action. The masses of all light valence quarks involved are extrapolated to their physical values.Comment: 8 Pages, 4 colour figures, Accepted for Publication in Phys.Lett.B. Typset in REVTeX 3.1 added figure and table with minor text modificatio

Two flavors of dynamical quarks on anisotropic lattices

We report on our study of two-flavor full QCD on anisotropic lattices using $O(a)$-improved Wilson quarks coupled with an RG-improved glue. The bare gauge and quark anisotropies corresponding to the renormalized anisotropy $\xi=a_s/a_t = 2$ are determined as functions of $\beta$ and $\kappa$, which covers the region of spatial lattice spacings $a_s\approx 0.28$--0.16 fm and $m_{PS}/m_V\approx 0.6$--0.9. The calibrations of the bare anisotropies are performed with the Wilson loop and the meson dispersion relation at 4 lattice cutoffs and 5--6 quark masses. Using the calibration results we calculate the meson mass spectrum and the Sommer scale $r_0$. We confirm that the values of $r_0$ calculated for the calibration using pseudo scalar and vector meson energy momentum dispersion relation coincide in the continuum limit within errors. This work serves to lay ground toward studies of heavy quark systems and thermodynamics of QCD including the extraction of the equation of state in the continuum limit using Wilson-type quark actions.Comment: 16 pages, 23 figures, Version accepted for publication in Physical Review

Chiral Lagrangian Parameters for Scalar and Pseudoscalar Mesons

The results of a high-statistics study of scalar and pseudoscalar meson propagators in quenched lattice QCD are presented. For two values of lattice spacing, $\beta=5.7$ ($a \approx .18$ fm) and 5.9 ($a \approx .12$ fm), we probe the light quark mass region using clover improved Wilson fermions with the MQA pole-shifting ansatz to treat the exceptional configuration problem. The quenched chiral loop parameters $m_0$ and $\alpha_{\Phi}$ are determined from a study of the pseudoscalar hairpin correlator. From a global fit to the meson correlators, estimates are obtained for the relevant chiral Lagrangian parameters, including the Leutwyler parameters $L_5$ and $L_8$. Using the parameters obtained from the singlet and nonsinglet pseudoscalar correlators, the quenched chiral loop effect in the nonsinglet scalar meson correlator is studied. By removing this QCL effect from the lattice correlator, we obtain the mass and decay constant of the ground state scalar, isovector meson $a_0$.Comment: 36 pages, 12 figures, LaTe

Flavor Singlet Meson Mass in the Continuum Limit in Two-Flavor Lattice QCD

We present results for the mass of the eta-prime meson in the continuum limit for two-flavor lattice QCD, calculated on the CP-PACS computer, using a renormalization-group improved gauge action, and Sheikholeslami and Wohlert's fermion action with tadpole-improved csw. Correlation functions are measured at three values of the coupling constant beta corresponding to the lattice spacing a approx. 0.22, 0.16, 0.11 fm and for four values of the quark mass parameter kappa corresponding to mpi over mrho approx. 0.8, 0.75, 0.7 and 0.6. For each beta, kappa pair, 400-800 gauge configurations are used. The two-loop diagrams are evaluated using a noisy source method. We calculate eta-prime propagators using local sources, and find that excited state contributions are much reduced by smearing. A full analysis for the smeared propagators gives metaprime=0.960(87)+0.036-0.248 GeV, in the continuum limit, where the second error represents the systematic uncertainty coming from varying the functional form for chiral and continuum extrapolations.Comment: 9 pages, 19 figures, 4 table

An Introductory Guide to Aligning Networks Using SANA, the Simulated Annealing Network Aligner.

Sequence alignment has had an enormous impact on our understanding of biology, evolution, and disease. The alignment of biological networks holds similar promise. Biological networks generally model interactions between biomolecules such as proteins, genes, metabolites, or mRNAs. There is strong evidence that the network topology-the "structure" of the network-is correlated with the functions performed, so that network topology can be used to help predict or understand function. However, unlike sequence comparison and alignment-which is an essentially solved problem-network comparison and alignment is an NP-complete problem for which heuristic algorithms must be used.Here we introduce SANA, the Simulated Annealing Network Aligner. SANA is one of many algorithms proposed for the arena of biological network alignment. In the context of global network alignment, SANA stands out for its speed, memory efficiency, ease-of-use, and flexibility in the arena of producing alignments between two or more networks. SANA produces better alignments in minutes on a laptop than most other algorithms can produce in hours or days of CPU time on large server-class machines. We walk the user through how to use SANA for several types of biomolecular networks

Thermodynamics of SU(3) gauge theory on anisotropic lattices

Finite temperature SU(3) gauge theory is studied on anisotropic lattices using the standard plaquette gauge action. The equation of state is calculated on $16^{3} \times 8$, $20^{3} \times 10$ and $24^{3} \times 12$ lattices with the anisotropy $\xi \equiv a_s / a_t = 2$, where $a_s$ and $a_t$ are the spatial and temporal lattice spacings. Unlike the case of the isotropic lattice on which $N_t=4$ data deviate significantly from the leading scaling behavior, the pressure and energy density on an anisotropic lattice are found to satisfy well the leading $1/N_t^2$ scaling from our coarsest lattice, $N_t/\xi=4$. With three data points at $N_t/\xi=4$, 5 and 6, we perform a well controlled continuum extrapolation of the equation of state. Our results in the continuum limit agree with a previous result from isotropic lattices using the same action, but have smaller and more reliable errors.Comment: RevTeX, 21 pages, 17 PS figures. A quantitative test about the benefit of anisotropic lattices added, minor errors corrected. Final version for PR