Folding and insertion thermodynamics of the transmembrane WALP peptide

The anchor of most integral membrane proteins consists of one or several helices spanning the lipid bilayer. The WALP peptide, GWW(LA)$_n$(L)WWA, is a common model helix to study the fundamentals of protein insertion and folding, as well as helix-helix association in the membrane. Its structural properties have been illuminated in a large number of experimental and simulation studies. In this combined coarse-grained and atomistic simulation study, we probe the thermodynamics of a single WALP peptide, focusing on both the insertion across the water-membrane interface, as well as folding in both water and a membrane. The potential of mean force characterizing the peptide's insertion into the membrane shows qualitatively similar behavior across peptides and three force fields. However, the Martini force field exhibits a pronounced secondary minimum for an adsorbed interfacial state, which may even become the global minimum---in contrast to both atomistic simulations and the alternative PLUM force field. Even though the two coarse-grained models reproduce the free energy of insertion of individual amino acids side chains, they both underestimate its corresponding value for the full peptide (as compared with atomistic simulations), hinting at cooperative physics beyond the residue level. Folding of WALP in the two environments indicates the helix as the most stable structure, though with different relative stabilities and chain-length dependence.Comment: 12 pages, 5 figure

Electrokinetic behavior of two touching inhomogeneous biological cells and colloidal particles: Effects of multipolar interactions

We present a theory to investigate electro-kinetic behavior, namely, electrorotation and dielectrophoresis under alternating current (AC) applied fields for a pair of touching inhomogeneous colloidal particles and biological cells. These inhomogeneous particles are treated as graded ones with physically motivated model dielectric and conductivity profiles. The mutual polarization interaction between the particles yields a change in their respective dipole moments, and hence in the AC electrokinetic spectra. The multipolar interactions between polarized particles are accurately captured by the multiple images method. In the point-dipole limit, our theory reproduces the known results. We find that the multipolar interactions as well as the spatial fluctuations inside the particles can affect the AC electrokinetic spectra significantly.Comment: Revised version with minor changes: References added and discussion extende

Lithium‐ion mobility in Li6B18(Li3N) and Li vacancy tuning in the solid solution Li6B18(Li3N)1−x(Li2O)x

All-solid-state batteries are promising candidates for safe energy-storage systems due to non-flammable solid electrolytes and the possibility to use metallic lithium as an anode. Thus, there is a challenge to design new solid electrolytes and to understand the principles of ion conduction on an atomic scale. We report on a new concept for compounds with high lithium ion mobility based on a rigid open-framework boron structure. The host–guest structure Li6B18(Li3N) comprises large hexagonal pores filled with urn:x-wiley:14337851:media:anie202213962:anie202213962-math-0001 Li7N] strands that represent a perfect cutout from the structure of α-Li3N. Variable-temperature 7Li NMR spectroscopy reveals a very high Li mobility in the template phase with a remarkably low activation energy below 19 kJ mol−1 and thus much lower than pristine Li3N. The formation of the solid solution of Li6B18(Li3N) and Li6B18(Li2O) over the complete compositional range allows the tuning of lithium defects in the template structure that is not possible for pristine Li3N and Li2O

Experimental and Computational Observations of Immunogenic Cobalt Porphyrin Lipid Bilayers: Nanodomain-Enhanced Antigen Association.

Cobalt porphyrin phospholipid (CoPoP) can incorporate within bilayers to enable non-covalent surface-display of antigens on liposomes by mixing with proteins bearing a polyhistidine tag (his-tag); however, the mechanisms for how this occurs are poorly understood. These were investigated using the his-tagged model antigen Pfs25, a protein antigen candidate for malaria transmission-blocking vaccines. Pfs25 was found to associate with the small molecule aquocobalamin, a form of vitamin B12 and a cobalt-containing corrin macrocycle, but without particle formation, enabling comparative assessment. Relative to CoPoP liposomes, binding and serum stability studies indicated a weaker association of Pfs25 to aquocobalamin or cobalt nitrilotriacetic acid (Co-NTA) liposomes, which have cobalt displayed in the aqueous phase on lipid headgroups. Antigen internalization by macrophages was enhanced with Pfs25 bound to CoPoP liposomes. Immunization in mice with Pfs25 bound to CoPoP liposomes elicited antibodies that recognized ookinetes and showed transmission-reducing activity. To explore the physical mechanisms involved, we employed molecular dynamics (MD) simulations of bilayers containing phospholipid, cholesterol, as well as either CoPoP or NTA-functionalized lipids. The results show that the CoPoP-containing bilayer creates nanodomains that allow access for a limited but sufficient amount of water molecules that could be replaced by his-tags due to their favorable free energy properties allowing for stabilization. The position of the metal center within the NTA liposomes was much more exposed to the aqueous environment, which could explain its limited capacity for stabilizing Pfs25. This study illustrates the impact of CoPoP-induced antigen particleization in enhancing vaccine efficacy, and provides molecular insights into the CoPoP bilayer properties that enable this

Dynamics of driven interfaces near isotropic percolation transition

We consider the dynamics and kinetic roughening of interfaces embedded in uniformly random media near percolation treshold. In particular, we study simple discrete ``forest fire'' lattice models through Monte Carlo simulations in two and three spatial dimensions. An interface generated in the models is found to display complex behavior. Away from the percolation transition, the interface is self-affine with asymptotic dynamics consistent with the Kardar-Parisi-Zhang universality class. However, in the vicinity of the percolation transition, there is a different behavior at earlier times. By scaling arguments we show that the global scaling exponents associated with the kinetic roughening of the interface can be obtained from the properties of the underlying percolation cluster. Our numerical results are in good agreement with theory. However, we demonstrate that at the depinning transition, the interface as defined in the models is no longer self-affine. Finally, we compare these results to those obtained from a more realistic reaction-diffusion model of slow combustion.Comment: 7 pages, 9 figures, to appear in Phys. Rev. E (1998

The source ambiguity problem: Distinguishing the effects of grammar and processing on acceptability judgments

Judgments of linguistic unacceptability may theoretically arise from either grammatical deviance or significant processing difficulty. Acceptability data are thus naturally ambiguous in theories that explicitly distinguish formal and functional constraints. Here, we consider this source ambiguity problem in the context of Superiority effects: the dispreference for ordering a wh-phrase in front of a syntactically “superior” wh-phrase in multiple wh-questions, e.g., What did who buy? More specifically, we consider the acceptability contrast between such examples and so-called D-linked examples, e.g., Which toys did which parents buy? Evidence from acceptability and self-paced reading experiments demonstrates that (i) judgments and processing times for Superiority violations vary in parallel, as determined by the kind of wh-phrases they contain, (ii) judgments increase with exposure, while processing times decrease, (iii) reading times are highly predictive of acceptability judgments for the same items, and (iv) the effects of the complexity of the wh-phrases combine in both acceptability judgments and reading times. This evidence supports the conclusion that D-linking effects are likely reducible to independently motivated cognitive mechanisms whose effects emerge in a wide range of sentence contexts. This in turn suggests that Superiority effects, in general, may owe their character to differential processing difficulty