Unfolding Simulations of Holomyoglobin from Four Mammals: Identification of Intermediates and β-Sheet Formation from Partially Unfolded States

Myoglobin (Mb) is a centrally important, widely studied mammalian protein. While much work has investigated multi-step unfolding of apoMb using acid or denaturant, holomyoglobin unfolding is poorly understood despite its biological relevance. We present here the first systematic unfolding simulations of holoMb and the first comparative study of unfolding of protein orthologs from different species (sperm whale, pig, horse, and harbor seal). We also provide new interpretations of experimental mean molecular ellipticities of myoglobin intermediates, notably correcting for random coil and number of helices in intermediates. The simulated holoproteins at 310 K displayed structures and dynamics in agreement with crystal structures (R g ~1.48-1.51 nm, helicity ~75%). At 400 K, heme was not lost, but some helix loss was observed in pig and horse, suggesting that these helices are less stable in terrestrial species. At 500 K, heme was lost within 1.0-3.7 ns. All four proteins displayed exponentially decaying helix structure within 20 ns. The C- and F-helices were lost quickly in all cases. Heme delayed helix loss, and sperm whale myoglobin exhibited highest retention of heme and D/E helices. Persistence of conformation (RMSD), secondary structure, and ellipticity between 2-11 ns was interpreted as intermediates of holoMb unfolding in all four species. The intermediates resemble those of apoMb notably in A and H helices, but differ substantially in the D-, E- and F-helices, which interact with heme. The identified mechanisms cast light on the role of metal/cofactor in poorly understood holoMb unfolding. We also observed β-sheet formation of several myoglobins at 500 K as seen experimentally, occurring after disruption of helices to a partially unfolded, globally disordered state; heme reduced this tendency and sperm-whale did not display any sheet propensity during the simulations

Measurement of b hadron lifetimes in exclusive decays containing a J/psi in p-pbar collisions at sqrt(s)=1.96TeV

We report on a measurement of $b$-hadron lifetimes in the fully reconstructed decay modes B^+ -->J/Psi K+, B^0 --> J/Psi K*, B^0 --> J/Psi Ks, and Lambda_b --> J/Psi Lambda using data corresponding to an integrated luminosity of 4.3 ${\rm fb}^{-1}$, collected by the CDF II detector at the Fermilab Tevatron. The measured lifetimes are $\tau$B^+ = $1.639 \pm 0.009 ({\rm stat}) \pm 0.009 {\rm (syst) ~ ps}$, $\tau$B^0 = $1.507 \pm 0.010 ({\rm stat}) \pm 0.008 {\rm (syst) ~ ps}$ and $\tau$Lambda_b = $1.537 \pm 0.045 ({\rm stat}) \pm 0.014 {\rm (syst) ~ ps}$. The lifetime ratios are $\tau$B^+/$\tau$B^0 = $1.088 \pm 0.009 ({\rm stat})\pm 0.004 ({\rm syst})$ and $\tau$Lambda_b/$\tau$B^0 = $1.020 \pm 0.030 ({\rm stat})\pm 0.008 ({\rm syst})$. These are the most precise determinations of these quantities from a single experiment.Comment: revised version. accepted for PRL publicatio

Search for High Mass Resonances Decaying to Muon Pairs in root s=1.96 TeV p(p)over-bar Collisions

We present a search for a new narrow, spin-1, high mass resonance decaying to mu(+)mu(-) + X, using a matrix-element-based likelihood and a simultaneous measurement of the resonance mass and production rate. In data with 4.6 fb(-1) of integrated luminosity collected by the CDF detector in p (p) over bar collisions at root s = 1960 GeV, the most likely signal cross section is consistent with zero at 16% confidence level. We therefore do not observe evidence for a high mass resonance and place limits on models predicting spin-1 resonances, including M > 1071 GeV/c(2) at 95% confidence level for a Z' boson with the same couplings to fermions as the Z boson

Measurement of b Hadron Lifetimes in Exclusive Decays Containing a J/Psi in p(p)over-bar Collisions at root s=1.96 TeV

We report on a measurement of b-hadron lifetimes in the fully reconstructed decay modes B+-> J/psi K+, B-0 -> J/psi K*(892)(0), B-0 -> J/psi K-s(0), and Lambda(0)(b)-> J/psi Lambda(0) using data corresponding to an integrated luminosity of 4.3 fb(-1), collected by the CDF II detector at the Fermilab Tevatron. The measured lifetimes are tau(B+)=[1.639 +/- 0.009(stat)+/- 0.009(syst)]ps, tau(B-0)=[1.507 +/- 0.010(stat)+/- 0.008(syst)]ps, and tau(Lambda(0)(b))=[1.537 +/- 0.045(stat)+/- 0.014(syst)]ps. The lifetime ratios are tau(B+)/tau(B-0)=[1.088 +/- 0.009(stat)+/- 0.004(syst)] and tau(Lambda(0)(b))/tau(B-0)=[1.020 +/- 0.030(stat)+/- 0.008(syst)]. These are the most precise determinations of these quantities from a single experiment