Kinetics of the helix-coil transition

Based on the Zimm-Bragg model we study cooperative helix-coil transition driven by a finite-speed change of temperature. There is an asymmetry between the coil-to-helix and helix-to-coil transition: the latter is displayed already for finite speeds, and takes shorter time than the former. This hysteresis effect has been observed experimentally, and it is explained here via quantifying system's stability in the vicinity of the critical temperature. A finite-speed cooling induces a non-equilibrium helical phase with the correlation length larger than in equilibrium. In this phase the characteristic length of the coiled domain and the non-equilibrium specific heat can display an anomalous response to temperature changes. Several pertinent experimental results on the kinetics helical biopolymers are discussed in detail.Comment: 6 pages, 8 figure

Thermal (in)stability of type I collagen fibrils

We measured Young's modulus at temperatures ranging from 20 to 100 ^{\circ}$C for a collagen fibril taken from rat's tendon. The hydration change under heating and the damping decrement were measured as well. At physiological temperatures$25-45^{\circ}$C Young's modulus decreases, which can be interpreted as instability of collagen. For temperatures between$45-80^{\circ}$C Young's modulus first stabilizes and then increases with decreasing the temperature. The hydrated water content and the damping decrement have strong maxima in the interval$70-80^{\circ}$C indicating on complex inter-molecular structural changes in the fibril. All these effects disappear after heat-denaturating the sample at$120^\circ$C. Our main result is a five-stage mechanism by which the instability of a single collagen at physiological temperatures is compensated by the interaction between collagen molecules within the fibril.Comment: 4 pages, 4 figure

Time-dependent coupled oscillator model for charged particle motion in the presence of a time varyingmagnetic field

The dynamics of time-dependent coupled oscillator model for the charged particle motion subjected to a time-dependent external magnetic field is investigated. We used canonical transformation approach for the classical treatment of the system, whereas unitary transformation approach is used when managing the system in the framework of quantum mechanics. For both approaches, the original system is transformed to a much more simple system that is the sum of two independent harmonic oscillators which have time-dependent frequencies. We therefore easily identified the wave functions in the transformed system with the help of invariant operator of the system. The full wave functions in the original system is derived from the inverse unitary transformation of the wave functions associated to the transformed system.Comment: 16 page

Universal geometrical factor of protein conformations as a consequence of energy minimization

The biological activity and functional specificity of proteins depend on their native three-dimensional structures determined by inter- and intra-molecular interactions. In this paper, we investigate the geometrical factor of protein conformation as a consequence of energy minimization in protein folding. Folding simulations of 10 polypeptides with chain length ranging from 183 to 548 residues manifest that the dimensionless ratio (V/(A)) of the van der Waals volume V to the surface area A and average atomic radius of the folded structures, calculated with atomic radii setting used in SMMP [Eisenmenger F., et. al., Comput. Phys. Commun., 138 (2001) 192], approach 0.49 quickly during the course of energy minimization. A large scale analysis of protein structures show that the ratio for real and well-designed proteins is universal and equal to 0.491\pm0.005. The fractional composition of hydrophobic and hydrophilic residues does not affect the ratio substantially. The ratio also holds for intrinsically disordered proteins, while it ceases to be universal for polypeptides with bad folding properties.Comment: 6 pages, 1 table, 4 figure

Molecular basis for passive immunotherapy of Alzheimer's disease

Amyloid aggregates of the amyloid-{beta} (A{beta}) peptide are implicated in the pathology of Alzheimer's disease. Anti-A{beta} monoclonal antibodies (mAbs) have been shown to reduce amyloid plaques in vitro and in animal studies. Consequently, passive immunization is being considered for treating Alzheimer's, and anti-A{beta} mAbs are now in phase II trials. We report the isolation of two mAbs (PFA1 and PFA2) that recognize A{beta} monomers, protofibrils, and fibrils and the structures of their antigen binding fragments (Fabs) in complex with the A{beta}(1–8) peptide DAEFRHDS. The immunodominant EFRHD sequence forms salt bridges, hydrogen bonds, and hydrophobic contacts, including interactions with a striking WWDDD motif of the antigen binding fragments. We also show that a similar sequence (AKFRHD) derived from the human protein GRIP1 is able to cross-react with both PFA1 and PFA2 and, when cocrystallized with PFA1, binds in an identical conformation to A{beta}(1–8). Because such cross-reactivity has implications for potential side effects of immunotherapy, our structures provide a template for designing derivative mAbs that target A{beta} with improved specificity and higher affinity

Hairy cell leukemia. Clinical recommendations

Hairy cell leukemia. Clinical recommendation