Four-states phase diagram of proteins

A four states phase diagram for protein folding as a function of temperature and solvent quality is derived from an improved 2-d lattice model taking into account the temperature dependence of the hydrophobic effect. The phase diagram exhibits native, globule and two coil-type regions. In agreement with experiment, the model reproduces the phase transitions indicative of both warm and cold denaturations. Finally, it predicts transitions between the two coil states and a critical point.Comment: 7 pages, 5 figures. Accepted for publication in Europhysics Letter

Sequencing of folding events in Go-like proteins

We have studied folding mechanisms of three small globular proteins: crambin (CRN), chymotrypsin inhibitor 2 (CI2) and the fyn Src Homology 3 domain (SH3) which are modelled by a Go-like Hamiltonian with the Lennard-Jones interactions. It is shown that folding is dominated by a well-defined sequencing of events as determined by establishment of particular contacts. The order of events depends primarily on the geometry of the native state. Variations in temperature, coupling strengths and viscosity affect the sequencing scenarios to a rather small extent. The sequencing is strongly correlated with the distance of the contacting aminoacids along the sequence. Thus $\alpha$-helices get established first. Crambin is found to behave like a single-route folder, whereas in CI2 and SH3 the folding trajectories are more diversified. The folding scenarios for CI2 and SH3 are consistent with experimental studies of their transition states.Comment: REVTeX, 12 pages, 11 EPS figures, J. Chem. Phys (in press

Role of framework mutations and antibody flexibility in the evolution of broadly neutralizing antibodies

Eliciting antibodies that are cross reactive with surface proteins of diverse strains of highly mutable pathogens (e.g., HIV, influenza) could be key for developing effective universal vaccines. Mutations in the framework regions of such broadly neutralizing antibodies (bnAbs) have been reported to play a role in determining their properties. We used molecular dynamics simulations and models of affinity maturation to study specific bnAbs against HIV. Our results suggest that there are different classes of evolutionary lineages for the bnAbs. If germline B cells that initiate affinity maturation have high affinity for the conserved residues of the targeted epitope, framework mutations increase antibody rigidity as affinity maturation progresses to evolve bnAbs. If the germline B cells exhibit weak/moderate affinity for conserved residues, an initial increase in flexibility via framework mutations may be required for the evolution of bnAbs. Subsequent mutations that increase rigidity result in highly potent bnAbs. Implications of our results for immunogen design are discussed

Breit interaction correction to the hyperfine constant of an external s-electron in many-electron atom

Correction to the hyperfine constant $A$ of an external s-electron in many-electron atom caused by the Breit interaction is calculated analytically: $\delta A/A =0.68 Z\alpha^2$. Physical mechanism for this correction is polarization of the internal electronic shells (mainly $1s^2$ shell) by the magnetic field of the external electron. This mechanism is similar to the polarization of vacuum considered by Karplus and Klein long time ago. The similarity is the reason why in both cases (Dirac sea polarization and internal atomic shells polarization) the corrections have the same dependence on the nuclear charge and fine structure constant. In conclusion we also discuss $Z\alpha^2$ corrections to the parity violation effects in atoms.Comment: 8 pages, 2 figure

Quantum Electrodynamics of the Helium Atom

Using singlet S states of the helium atom as an example, I describe precise calculation of energy levels in few-electron atoms. In particular, a complete set of effective operators is derived which generates O(m*alpha^6) relativistic and radiative corrections to the Schr"odinger energy. Average values of these operators can be calculated using a variational Schr"odinger wave function.Comment: 23 pages, revte

Theory of Anomalous Hall Effect in a Heavy fermion System with a Strong Anisotropic Crystal Field

In a heavy fermion system, there exists the anomalous Hall effect caused by localized $f$-orbital freedom, in addition to the normal Hall effect due to the Lorentz force. In 1994, we found that the Hall coefficient caused by the anomalous Hall effect ($R_H^{AHE}$) is predominant and the relation $R_H^{AHE} \propto \rho^2$ ($\rho$ is the electrical resistivity) holds at low temperatures in many compounds. In this work, we study the system where the magnetic susceptibility is highly anisotropic due to the strong crystalline electric field on $f$-orbitals. Interestingly, we find that $R_H^{AHE}$ is nearly isotropic in general. This tendency is frequently observed experimentally, which has casted suspicion that the anomalous Hall effect may be irrelevant in real materials. Our theory corresponds to corrections and generalizations of the pioneering work on ferromagnetic metals by Karplus and Luttinger.Comment: 4 pages, revtex, to be published in J. Phys. Soc. Jpn. (No.8

Dynamics of semiclassical Bloch wave - packets

The semiclassical approximation for electron wave-packets in crystals leads to equations which can be derived from a Lagrangian or, under suitable regularity conditions, in a Hamiltonian framework. In the plane, these issues are studied %in presence of external fields using the method of the coadjoint orbit applied to the ``enlarged'' Galilei group.Comment: 15 pages, Talk given at Nonlinear Physics. Theory and Experiment. IV,Gallipoli (Lecce), Italy - June 22 - July 1, 200

Anomalous Hall Effect and Skyrmion Number in Real- and Momentum-space

We study the anomalous Hall effect (AHE) for the double exchange model with the exchange coupling $|J_H|$ being smaller than the bandwidth $|t|$ for the purpose of clarifying the following unresolved and confusing issues: (i) the effect of the underlying lattice structure, (ii) the relation between AHE and the skyrmion number, (iii) the duality between real and momentum spaces, and (iv) the role of the disorder scatterings; which is more essential, $\sigma_H$ (Hall conductivity) or $\rho_H$ (Hall resistivity)? Starting from a generic expression for $\sigma_H$, we resolve all these issues and classify the regimes in the parameter space of $J_H \tau$ ($\tau$: elastic-scattering time), and $\lambda_{s}$ (length scale of spin texture). There are two distinct mechanisms of AHE; one is characterized by the real-space skyrmion-number, and the other by momentum-space skyrmion-density at the Fermi level, which work in different regimes of the parameter space.Comment: 4 pages, 1 figure, REVTe

Conformations of Proteins in Equilibrium

We introduce a simple theoretical approach for an equilibrium study of proteins with known native state structures. We test our approach with results on well-studied globular proteins, Chymotrypsin Inhibitor (2ci2), Barnase and the alpha spectrin SH3 domain and present evidence for a hierarchical onset of order on lowering the temperature with significant organization at the local level even at high temperatures. A further application to the folding process of HIV-1 protease shows that the model can be reliably used to identify key folding sites that are responsible for the development of drug resistance .Comment: 6 pages, 3 eps figure