The human platelet antigen-1b (Pro) variant of αβ allosterically shifts the dynamic conformational equilibrium of this integrin toward the active state.

Integrins are heterodimeric cell-adhesion receptors comprising α and β subunits that transmit signals allosterically in both directions across the membrane by binding to intra- and extracellular components. The human platelet antigen-1 (HPA-1) polymorphism in αβ arises from a Leu → Pro exchange at residue 33 in the genu of the β subunit, resulting in Leu (HPA-1a) or Pro (HPA-1b) isoforms. Although clinical investigations have provided conflicting results, some studies have suggested that Pro platelets exhibit increased thrombogenicity.

Identification of a Conserved Interface of Human Immunodeficiency Virus Type 1 and Feline Immunodeficiency Virus Vifs with Cullin 5.

Members of the apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC3 [A3]) family of DNA cytidine deaminases are intrinsic restriction factors against retroviruses. In felids such as the domestic cat (), the A3 genes encode the A3Z2, A3Z3, and A3Z2Z3 antiviral cytidine deaminases. Only A3Z3 and A3Z2Z3 inhibit viral infectivity factor (Vif)-deficient feline immunodeficiency virus (FIV).

Biomolecular coevolution and its applications: Going from structure prediction toward signaling, epistasis, and function.

Evolution leads to considerable changes in the sequence of biomolecules, while their overall structure and function remain quite conserved. The wealth of genomic sequences, the 'Biological Big Data', modern sequencing techniques provide allows us to investigate biomolecular evolution with unprecedented detail. Sophisticated statistical models can infer residue pair mutations resulting from spatial proximity.

Review of lattice results concerning low-energy particle physics: Flavour Lattice Averaging Group (FLAG).

We review lattice results related to pion, kaon, - and -meson physics with the aim of making them easily accessible to the particle-physics community. More specifically, we report on the determination of the light-quark masses, the form factor [Formula: see text], arising in the semileptonic [Formula: see text] transition at zero momentum transfer, as well as the decay constant ratio [Formula: see text] and its consequences for the CKM matrix elements [Formula: see text] and [Formula: see text]. Furthermore, we describe the results obtained on the lattice for some of the low-energy constants of [Formula: see text] and [Formula: see text] Chiral Perturbation Theory.

Tertiary Interactions in the Unbound Guanine-Sensing Riboswitch Focus Functional Conformational Variability on the Binding Site.

Riboswitches are genetic regulatory elements mainly found in bacteria, which regulate gene expression based on the availability of a ligand. Purine-sensing riboswitches, including the guanine-sensing riboswitch (Gsw), possess tertiary interactions connecting the L2 and L3 loops. These interactions are important for ligand binding to the aptamer.

QCD Coupling from a Nonperturbative Determination of the Three-Flavor Λ Parameter.

We present a lattice determination of the Λ parameter in three-flavor QCD and the strong coupling at the Z pole mass. Computing the nonperturbative running of the coupling in the range from 0.2 to 70 GeV, and using experimental input values for the masses and decay constants of the pion and the kaon, we obtain Λ_{MS[over ¯]}^{(3)}=341(12)  MeV.

Contribution of single amino acid and codon substitutions to the production and secretion of a lipase by Bacillus subtilis.

Background: Bacillus subtilis produces and secretes proteins in amounts of up to 20 g/l under optimal conditions. However, protein production can be challenging if transcription and cotranslational secretion are negatively affected, or the target protein is degraded by extracellular proteases. This study aims at elucidating the influence of a target protein on its own production by a systematic mutational analysis of the homologous B.

On the potential alternate binding change mechanism in a dimeric structure of Pyruvate Phosphate Dikinase.

The pyruvate phosphate dikinase (PPDK) reaction mechanism is characterized by a distinct spatial separation of reaction centers and large conformational changes involving an opening-closing motion of the nucleotide-binding domain (NBD) and a swiveling motion of the central domain (CD). However, why PPDK is active only in a dimeric form and to what extent an alternate binding change mechanism could underlie this fact has remained elusive. We performed unbiased molecular dynamics simulations, configurational free energy computations, and rigidity analysis to address this question.

Determination of the QCD Λ Parameter and the Accuracy of Perturbation Theory at High Energies.

We discuss the determination of the strong coupling α_{MS[over ¯]}(m_{Z}) or, equivalently, the QCD Λ parameter. Its determination requires the use of perturbation theory in α_{s}(μ) in some scheme s and at some energy scale μ. The higher the scale μ, the more accurate perturbation theory becomes, owing to asymptotic freedom.

Constraints on phase stability, defect energies, and elastic constants of metals described by EAM-type potentials.

We demonstrate that the embedded-atom method and related potentials predict many dimensionless properties of simple metals to depend predominantly on a single coefficient μ, which typically lies between 0.3 and 0.45.

Chiral symmetry breaking in QCD with two light flavors.

A distinctive feature of the presence of spontaneous chiral symmetry breaking in QCD is the condensation of low modes of the Dirac operator near the origin. The rate of condensation must be equal to the slope of M(π)(2)F(π)(2)/2 with respect to the quark mass m in the chiral limit, where M(π) and F(π) are the mass and the decay constant of the Nambu-Goldstone bosons. We compute the spectral density of the (Hermitian) Dirac operator, the quark mass, the pseudoscalar meson mass, and decay constant by numerical simulations of lattice QCD with two light degenerate Wilson quarks.

Effects of heavy sea quarks at low energies.

We present a factorization formula for the dependence of light hadron masses and low energy hadronic scales on the mass M of a heavy quark: apart from an overall mass-independent factor Q, ratios such as r_{0}(M)/r_{0}(0) are computable in perturbation theory at large M. The perturbation theory part is stable concerning different loop orders. Our nonperturbative Monte Carlo results obtained in a model calculation, where a doublet of heavy quarks is decoupled, match quantitatively to the perturbative prediction.

Logarithmic corrections in (4+1) -dimensional directed percolation.

We simulate directed site percolation on two lattices with four spatial and one timelike dimensions (simple and body-centered hypercubic in space) with the standard single cluster spreading scheme. For efficiency, the code uses the same ingredients (hashing, histogram reweighing, and improved estimators) as described by Grassberger [Phys. Rev.

Folding proteins by first-passage-times-optimized replica exchange.

Replica exchange simulations have become the method of choice in computational protein science, but they still often do not allow an efficient sampling of low-energy protein configurations. Here, we reconstruct replica flow in the temperature ladder from first passage times and use it for temperature optimization, thereby maximizing sampling. The method is applied in simulations of folding thermodynamics for a number of proteins starting from the pentapeptide Met-enkephalin, through the 36-residue HP-36, up to the 67-residue protein GS-alpha3W.

Optimized explicit-solvent replica exchange molecular dynamics from scratch.

Replica exchange molecular dynamics (REMD) simulations have become an important tool to study proteins and other biological molecules in silico. However, such investigations require considerable, and often prohibitive, numerical effort when the molecules are simulated in explicit solvents. In this communication we show that in this case the cost can be minimized by choosing the number of replicas as N(opt) approximately 1+0.

The Alzheimer's beta amyloid (Abeta1-39) monomer in an implicit solvent.

Results from replica-exchange and regular room temperature molecular dynamics simulations of the Alzheimer's beta amyloid (Abeta(1-39)) monomer in an implicit solvent are reported. Our data indicate that at room temperature, the monomer assumes random-coil and soluble conformations. No beta content is observed which therefore seems to be a product of oligomerization and aggregation of monomers.

Simulation of Top7-CFr: a transient helix extension guides folding.

Protein structures often feature beta-sheets in which adjacent beta-strands have large sequence separation. How the folding process orchestrates the formation and correct arrangement of these strands is not comprehensively understood. Particularly challenging are proteins in which beta-strands at the N and C termini are neighbors in a beta-sheet.

Optimizing replica exchange moves for molecular dynamics.

We sketch the statistical physics framework of the replica exchange technique when applied to molecular dynamics simulations. In particular, we draw attention to generalized move sets that allow a variety of optimizations as well as new applications of the method.

Efficient parallel tempering for first-order phase transitions.

We present a Monte Carlo algorithm that facilitates efficient parallel tempering simulations of the density of states g(E) . We show that the algorithm eliminates the supercritical slowing down in the case of the Q=20 and Q=256 Potts models in two dimensions, typical examples for systems with extreme first-order phase transitions. As recently predicted, and shown here, the microcanonical heat capacity along the calorimetric curve has negative values for finite systems.

Ring polymer simulations with global radius of curvature.

We simulate three-dimensional flexible off-lattice ring polymers of length L up to L=4000 for various values of the global radius of curvature Rgrc=0.25 , 0.48, and 1.

Aggregation of beta-amyloid fragments.

The authors study the folding and aggregation of six chains of the beta-amyloid fragment 16-22 using Monte Carlo simulations. While the isolated fragment prefers a helical form at room temperature, in the system of six interacting fragments one observes both parallel and antiparallel beta sheets below a crossover temperature T(x) approximately equal to 420 K. The antiparallel sheets have lower energy and are therefore more stable.

Fast and accurate determination of the Wigner rotation matrices in the fast multipole method.

In the rotation based fast multipole method the accurate determination of the Wigner rotation matrices is essential. The combination of two recurrence relations and the control of the error accumulations allow a very precise determination of the Wigner rotation matrices. The recurrence formulas are simple, efficient, and numerically stable.

Monte Carlo algorithm for least dependent non-negative mixture decomposition.

We propose a simulated annealing algorithm (stochastic non-negative independent component analysis, SNICA) for blind decomposition of linear mixtures of non-negative sources with non-negative coefficients. The demixing is based on a Metropolis-type Monte Carlo search for least dependent components, with the mutual information between recovered components as a cost function and their non-negativity as a hard constraint. Elementary moves are shears in two-dimensional subspaces and rotations in three-dimensional subspaces.

Improved spatial characterization of the epileptic brain by focusing on nonlinearity.

An advanced characterization of the complicated dynamical system brain is one of science's biggest challenges. Nonlinear time series analysis allows characterizing nonlinear dynamical systems in which low-dimensional nonlinearity gives rise to complex and irregular behavior. While several studies indicate that nonlinear methods can extract valuable information from neuronal dynamics, others doubt their necessity and conjecture that the same information can be obtained using classical linear techniques.