Structural Dynamics and Catalytic Mechanism of ATP13A2 (PARK9) from Simulations

ATP13A2 is a gene encoding a protein of the P5B subfamily of ATPases and is a PARK gene. Molecular defects of the gene are mainly associated with variations of Parkinson’s disease (PD). Despite the established importance of the protein in regulating neuronal integrity, the three-dimensional structure of the protein currently remains unresolved crystallographically. We have modeled the structure and reactivity of the full-length protein in its E1-ATP state. Using molecular dynamics (MD), quantum cluster, and quantum mechanical/molecular mechanical (QM/MM) methods, we aimed at describing the main catalytic reaction, leading to the phosphorylation of Asp513. Our MD simulations suggest that two positively charged Mg2+ cations are present at the active site during the catalytic reaction, stabilizing a specific triphosphate binding mode. Using QM/MM calculations, we subsequently calculated the reaction profiles for the phosphoryl transfer step in the presence of one and two Mg2+ cations. The calculated barrier heights in both cases are found to be ∼12.5 and 7.5 kcal mol–1, respectively. We elucidated details of the catalytically competent ATP conformation and the binding mode of the second Mg2+ cofactor. We also examined the role of the conserved Arg686 and Lys859 catalytic residues. We observed that by significantly lowering the barrier height of the ATP cleavage reaction, Arg686 had major effect on the reaction. The removal of Arg686 increased the barrier height for the ATP cleavage by more than 5.0 kcal mol–1 while the removal of key electrostatic interactions created by Lys859 to the γ-phosphate and Asp513 destabilizes the reactant state. When missense mutations occur in close proximity to an active site residue, they can interfere with the barrier height of the reaction, which can halt the normal enzymatic rate of the protein. We also found large binding pockets in the full-length structure, including a transmembrane domain pocket, which is likely where the ATP13A2 cargo binds

Quark matter in compact stars?

Ozel, in a recent reanalysis of EXO 0748-676 observational data (astro-ph/0605106), concluded that quark matter probably does not exist in the center of compact stars. We show that the data is actually consistent with the presence of quark matter in compact stars.Comment: 4 pages, LaTeX; New title and overall rewrite to reflect version published in Nature. Conclusions unchange

1-2-3-flavor color superconductivity in compact stars

We suggest a scenario where the three light quark flavors are sequentially deconfined under increasing pressure in cold asymmetric nuclear matter, e.g., as in neutron stars. The basis for our analysis is a chiral quark matter model of Nambu--Jona-Lasinio (NJL) type with diquark pairing in the spin-1 single flavor (CSL) and spin-0 two/three flavor (2SC/CFL) channels, and a Dirac-Brueckner Hartree-Fock (DBHF) approach in the nuclear matter sector. We find that nucleon dissociation sets in at about the saturation density, n_0, when the down-quark Fermi sea is populated (d-quark dripline) due to the flavor asymmetry imposed by beta-equilibrium and charge neutrality. At about 3n_0 u-quarks appear forming a two-flavor color superconducting (2SC) phase, while the s-quark Fermi sea is populated only at still higher baryon density. The hybrid star sequence has a maximum mass of 2.1 M_sun. Two- and three-flavor quark matter phases are found only in gravitationally unstable hybrid star solutions.Comment: 4 pages, 2 figures, to appear in the proceedings of Quark Matter 2008: 20th International Conference on Ultra-Relativistic Nucleus Nucleus Collisions (QM 2008), Jaipur, India, 4-10 Feb 200

Heavy Ion Collisions at Relativistic Energies: Testing a Nuclear Matter at High Baryon and Isospin Density

We show that the phenomenology of isospin effects on heavy ion reactions at intermediate energies (few AGeV range) is extremely rich and can allow a ``direct'' study of the covariant structure of the isovector interaction in the hadron medium. We work within a relativistic transport frame, beyond a cascade picture, consistently derived from effective Lagrangians, where isospin effects are accounted for in the mean field and collision terms. Rather sensitive observables are proposed from collective flows (``differential'' flows) and from pion/kaon production ($\pi^-/\pi^+$, $K^0/K^+$ yields). For the latter point relevant non-equilibrium effects are stressed. The possibility of the transition to a mixed hadron-quark phase, at high baryon and isospin density, is finally suggested. Some signatures could come from an expected ``neutron trapping'' effect.Comment: 8 pages, 4 figures, espcrc1 (latex) style. Conf. "Perspectives in Hadronic Physics", ICTP Trieste May 2006, Nucl.Phys. A, to appea

Equation of State of Nuclear Matter at high baryon density

A central issue in the theory of astrophysical compact objects and heavy ion reactions at intermediate and relativistic energies is the Nuclear Equation of State (EoS). On one hand, the large and expanding set of experimental and observational data is expected to constrain the behaviour of the nuclear EoS, especially at density above saturation, where it is directly linked to fundamental processes which can occur in dense matter. On the other hand, theoretical predictions for the EoS at high density can be challenged by the phenomenological findings. In this topical review paper we present the many-body theory of nuclear matter as developed along different years and with different methods. Only nucleonic degrees of freedom are considered. We compare the different methods at formal level, as well as the final EoS calculated within each one of the considered many-body schemes. The outcome of this analysis should help in restricting the uncertainty of the theoretical predictions for the nuclear EoS.Comment: 51 pages, to appear in J. Phys. G as Topical Revie

Strange Exotic States and Compact Stars

We discuss the possible appearance of strange exotic multi-quark states in the interior of neutron stars and signals for the existence of strange quark matter in the core of compact stars. We show how the in-medium properties of possible pentaquark states are constrained by pulsar mass measurements. The possibility of generating the observed large pulsar kick velocities by asymmetric emission of neutrinos from strange quark matter in magnetic fields is outlined.Comment: 10 pages, invited talk given at the International Conference on Strangeness in Quark Matter 2006 (SQM2006), UCLA, USA, March 26-31, 2006, Journal of Physics G in press, refs. adde

Core collapse supernovae in the QCD phase diagram

We compare two classes of hybrid equations of state with a hadron-to-quark matter phase transition in their application to core collapse supernova simulations. The first one uses the quark bag model and describes the transition to three-flavor quark matter at low critical densities. The second one employs a Polyakov-loop extended Nambu-Jona-Lasinio (PNJL) model with parameters describing a phase transition to two-flavor quark matter at higher critical densities. These models possess a distinctly different temperature dependence of their transition densities which turns out to be crucial for the possible appearance of quark matter in supernova cores. During the early post bounce accretion phase quark matter is found only if the phase transition takes place at sufficiently low densities as in the study based on the bag model. The increase critical density with increasing temperature, as obtained for our PNJL parametrization, prevents the formation of quark matter. The further evolution of the core collapse supernova as obtained applying the quark bag model leads to a structural reconfiguration of the central proto-neutron star where, in addition to a massive pure quark matter core, a strong hydrodynamic shock wave forms and a second neutrino burst is released during the shock propagation across the neutrinospheres. We discuss the severe constraints in the freedom of choice of quark matter models and their parametrization due to the recently observed 2 solar mass pulsar and their implications for further studies of core collapse supernovae in the QCD phase diagram.Comment: 19 pages, 4 figures, CPOD2010 conference proceedin

How strange are compact star interiors ?

We discuss a Nambu--Jona-Lasinio (NJL) type quantum field theoretical approach to the quark matter equation of state with color superconductivity and construct hybrid star models on this basis. It has recently been demonstrated that with increasing baryon density, the different quark flavors may occur sequentially, starting with down-quarks only, before the second light quark flavor and at highest densities also the strange quark flavor appears. We find that color superconducting phases are favorable over non-superconducting ones which entails consequences for thermodynamic and transport properties of hybrid star matter. In particular, for NJL-type models no strange quark matter phases can occur in compact star interiors due to mechanical instability against gravitational collapse, unless a sufficiently strong flavor mixing as provided by the Kobayashi-Maskawa-'t Hooft determinant interaction is present in the model. We discuss observational data on mass-radius relationships of compact stars which can put constraints on the properties of dense matter equation of state.Comment: 7 pages, 2 figures, to appear in the Proceedings of the International Conference SQM2009, Buzios, Rio de Janeiro, Brazil, Sep.27-Oct.2, 200

Isospin Effects on Strangeness in Heavy-Ion Collisions

Kaon properties are studied within the framework of a fully covariant transport approach. The kaon-nucleon potential is evaluated in two schemes, a chiral perturbative approach and an effective One-Boson-Exchange model. Isospin effects are explicitly accounted for in both models. The transport calculations indicate a significant sensitivity of momentum distributions and total yields of $K^{0,+}$ isospin states on the choice of the kaon-nucleon interaction. Furthermore, isospin effects are rather moderate on absolute kaon yields, but appear on strangeness ratios. This is an important issue in determining the high density symmetry energy from studies of strangeness production in heavy-ion collisions.Comment: 15 papes, 5 figures. Accepted for publication in Nuclear Physic