Three-level Doppler-free two- and three-photon resonances

Summary We analyse saturated-absorption and two-photon absorption line shapes in Doppler-broadened three-level systems with nearly degenerate resonance frequencies. The two counterpropagating equal-frequency laser beams of arbitrary intensity irradiating the sample are allowed to couple to both atomic transitions. Various Doppler-free resonances associated to two- and three-photon effects occur. Their saturating behaviour is analysed. A comparison is made with experiments by Woerdmann and Schuurmans and by Himbertet al. To speed up publication, the authors of this paper have agreed to not receive the proofs for correction.     

Macromolecular Crowding and the Sizes of Neutral Flexible Polymer Chains: The Role of Colloids Sizes and Concentrations

In the present work, we revisit the effect of macromolecular crowding on the sizes of flexible neutral polymer chains. Motivated by recent experimental measurements on crowding effects on neutral flexible polymers chains, we perform Monte Carlo simulations on a model system consisting of hard spheres (HS) and a neutral flexible polymer chain. We find that, depending on the ratio of the sizes of the colloidal particles to the sizes of the polymer chain, and thus, on the extent of the colloid partitioning among the chain segments and the solution, the flexible polymeric coil may be either continuously compressed, or initially compressed followed by a reswelling at high enough colloid concentration. The chain behavior is thus nonmonotonic, a point which, apart from the work of Khalatur et al., has not so far been stressed in simulations of flexible polymer chains under crowding conditions. A thermodynamic model for the polymer–colloid interactions based on the Gibbs–Duhem equation and on a “Flory‐type” argument is also presented, emphasizing the indirect influence of macromolecular crowding on the monomers chemical potential. We show explicitly that under crowding conditions, the colloids are driven into the most compact coil states. These analytical results are compared with the results of the potential of mean force between the chain center of mass and the colloids obtained from the Monte Carlo simulations, and a reasonable agreement is found. The implications of the aforementioned results are further discussed in the context of biological systems, specially those for which macromolecular crowding is supposed to play the important role of including preferentially other (charged) macromolecules into the colloid‐compressed polymer phase.

     

Drug–protein interaction with Vpu from HIV-1: proposing binding sites for amiloride and one of its derivatives

Vpu is an 81-amino-acid auxiliary protein of the genome of HIV-1. It is proposed that one of its roles is to enhance particle release by self-assembling to form water-filled channels enabling the flux of ions at the site of the plasma membrane of the infected cell. Hexamethylene amiloride has been shown to block Vpu channel activity when the protein is reconstituted into lipid bilayers. In a docking approach with monomeric, pentameric and hexameric bundle models of Vpu corresponding to the transmembrane part of the protein, a putative binding site of hexamethylene amiloride is proposed and is compared with the site for the nonpotent amiloride. The binding mode for both ligands is achieved by optimizing hydrogen bond interactions with serines. Binding energies and binding constants are the lowest for protonated hexamethylene amiloride in the pentameric bundle. Figure The proposed binding site of the Vpu channel blocker hexamethylene amiloride within the lumen of the Vpu bundle. The bundle is a homo-pentamer with each monomer consisting of the first 32 amino acids of Vpu including the transmembrane part of the protein which is encoded by HIV-1. The bundle atoms are shown in their van der Waals representation and the helix backbone in a ribbon representation. Residues Trp-23 and Ser-24 are highlighted as sticks. Hexamethylene amiloride is shown in yellow (C atoms) and blue (N atoms)