Evaluating the transferability of coarse-grained, density-dependent implicit solvent models to mixtures and chains

Previously, we described a coarse-graining method for creating local density-dependent implicit solvent (DDIS) potentials that reproduce the radial distribution function (RDF) and solute excess chemical potential across a range of particle concentrations [ E. C. Allen and G. C. Rutledge, J. Chem. Phys. 128, 154115 (2008) ]. In this work, we test the transferability of these potentials, derived from simulations of monomeric solute in monomeric solvent, to mixtures of solutes and to solute chains in the same monomeric solvent. For this purpose, “transferability” refers to the predictive capability of the potentials without additional optimization. We find that RDF transferability to mixtures is very good, while RDF errors in systems of chains increase linearly with chain length. Excess chemical potential transferability is good for mixtures at low solute concentration, chains, and chains of mixed composition; at higher solute concentrations in mixtures, chemical potential transferability fails due to the nature of the DDIS potentials, in which particle insertion directly affects the interaction potential. With these results, we demonstrate that DDIS potentials derived for pure solutes can be used effectively in the study of many important systems including those involving mixtures, chains, and chains of mixed composition in monomeric solvent.United States. Dept. of Energy (Computational Sciences Graduate Fellowship

Stability of an Exciton bound to an Ionized Donor in Quantum Dots

Total energy, binding energy, recombination rate (of the electron hole pair) for an exciton (X) bound in a parabolic two dimensional quantum dot by a donor impurity located on the z axis at a distance d from the dot plane, are calculated by using the Hartree formalism with a recently developed numerical method (PMM) for the solution of the Schroedinger equation. As our analysis indicates there is a critical dot radius such that for radius less than the critical radius the complex is unstable and with an increase of the impurity distance this critical radius increases. Furthermore, there is a critical value of the mass ratio such that for mass ratio less than the critical value the complex is stable. The appearance of this stability condition depends both on the impurity distance and the dot radius, in a way that with an increase of the impurity distance we have an increase in the maximum dot radius where this stability condition appears. For dot radii greater than this maximum dot radius (for fixed impurity distance) the complex is always stable.Comment: 17 pages, 7 figures Applying a new numerical method which is based on the adiabatic stability of quantum mechanics, we study the stability of an exciton (X) bound in a parabolic two dimensional quantum dot by a donor impurity located on the z axis at a distance d from the dot plan

What information theory can tell us about quantum reality

An investigation of Einstein's ``physical'' reality and the concept of quantum reality in terms of information theory suggests a solution to quantum paradoxes such as the Einstein-Podolsky-Rosen (EPR) and the Schroedinger-cat paradoxes. Quantum reality, the picture based on unitarily evolving wavefunctions, is complete, but appears incomplete from the observer's point of view for fundamental reasons arising from the quantum information theory of measurement. Physical reality, the picture based on classically accessible observables is, in the worst case of EPR experiments, unrelated to the quantum reality it purports to reflect. Thus, quantum information theory implies that only correlations, not the correlata, are physically accessible: the mantra of the Ithaca interpretation of quantum mechanics.Comment: LaTeX with llncs.cls, 11 pages, 6 postscript figures, Proc. of 1st NASA Workshop on Quantum Computation and Quantum Communication (QCQC 98

Novel highly potent CD4bs bNAb with restricted pathway to HIV-1 escape

Purpose: Broadly HIV-1 neutralizing antibodies (bNAbs) can suppress viremia in humans and represent a novel approach for effective immunotherapy. However, bNAb monotherapy selects for antibody-resistant viral variants. Thus, we focused on the identification of new antibody combinations and/or novel bNAbs that restrict pathways of HIV-1 escape. Methods: We screened HIV-1 positive patients for their neutralizing capacities. Following, we performed single cell sorting and PCR of HIV-1 Env-reactive mature B cells of identified elite neutralizers. Found antibodies were tested for neutralization and binding capacities in vitro. Further, their antiviral activity was tested in an HIV-1 infected humanized mouse model. Results: Here we report the isolation of antibody 1–18, a VH1–46-encoded CD4 binding site (CD4bs) bNAb identified in an individual ranking among the top 1% neutralizers of 2,274 HIV-1-infected subjects. Tested on a 119-virus panel, 1–18 showed to be exceptionally broad and potent with a coverage of 97% and a mean IC50 of 0.048 lg/mL, exceeding the activity of most potent CD4bs bNAbs described to-date. A 2.4 Å cryo-EM structure of 1–18 bound to a native-like Env trimer revealed that it interacts with HIV-1 env similar to other CD4bs bNAbs, but includes additional contacts to the V3 loop of the adjacent protomer. Notably, in vitro, 1–18 maintained activity against viruses carrying mutations associated with escape from VRC01-class bNAbs. Further, its HIV-1 env wide escape profile differed critically from other CD4bs bNAbs. In humanized mice, monotherapy with 1–18 was sufficient to prevent the development of viral escape variants that rapidly emerged during treatment with other CD4bs bNAbs. Finally, 1–18 overcame classical HIV-1 mutations that are driven by VRC01-like bNAbs in vivo. Conclusion: 1–18 is a highly potent and broad bNAb that restricts escape and overcomes frequent CD4bs escape pathways, providing new options for bNAb combinations to prevent and treat HIV-1 infection

Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody

Broadly neutralizing antibodies (bNAbs) represent a promising approach to prevent and treat HIV-1 infection. However, viral escape through mutation of the HIV-1 envelope glycoprotein (Env) limits clinical applications. Here we describe 1-18, a new V_H1-46-encoded CD4 binding site (CD4bs) bNAb with outstanding breadth (97%) and potency (GeoMean IC₅₀ = 0.048 μg/mL). Notably, 1-18 is not susceptible to typical CD4bs escape mutations and effectively overcomes HIV-1 resistance to other CD4bs bNAbs. Moreover, mutational antigenic profiling uncovered restricted pathways of HIV-1 escape. Of most promise for therapeutic use, even 1-18 alone fully suppressed viremia in HIV-1-infected humanized mice without selecting for resistant viral variants. A 2.5-Å cryo-EM structure of a 1-18-BG505_(SOSIP.664) Env complex revealed that these characteristics are likely facilitated by a heavy-chain insertion and increased inter-protomer contacts. The ability of 1-18 to effectively restrict HIV-1 escape pathways provides a new option to successfully prevent and treat HIV-1 infection