A combined treatment of hydration and dynamical effects for the modeling of host–guest binding thermodynamics: the SAMPL5 blinded challenge

As part of the SAMPL5 blinded experiment, we computed the absolute binding free energies of 22 host–guest complexes employing a novel approach based on the BEDAM single-decoupling alchemical free energy protocol with parallel replica exchange conformational sampling and the AGBNP2 implicit solvation model specifically customized to treat the effect of water displacement as modeled by the Hydration Site Analysis method with explicit solvation. Initial predictions were affected by the lack of treatment of ionic charge screening, which is very significant for these highly charged hosts, and resulted in poor relative ranking of negatively versus positively charged guests. Binding free energies obtained with Debye–Hückel treatment of salt effects were in good agreement with experimental measurements. Water displacement effects contributed favorably and very significantly to the observed binding affinities; without it, the modeling predictions would have grossly underestimated binding. The work validates the implicit/explicit solvation approach employed here and it shows that comprehensive physical models can be effective at predicting binding affinities of molecular complexes requiring accurate treatment of conformational dynamics and hydration.     

Jump conditions across strong compaction waves in gas saturated rigid porous media

Based on experimental results and some additional simplifying assumptions, the general macroscopic two phase equations governing the flow field which is developed in a gas saturated rigid porous medium domain were simplified to a form which enab led us to develop two analytical models for calculating the jump conditions across strong compaction waves.Predictions obtained by these two simplified analytical models are compared to the experimental results of Sandusky and Liddiard (1985) and to predictions of another more complicated model which was proposed by Powers et al. (1989). Fairly good to excelle nt agreements are evident.This article was processed using Springer-Verlag T_EX Shock Waves macro package 1.0 and the AMS fonts, developed by the American Mathematical Society.     

Numerical investigation of the propagation of shock waves in rigid porous materials: flow field behavior and parametric study

A numerical parametric study of the flow field which develops when a planar shock wave impinge on a rigid porous material is presented. This study complements an earlier study (Levy et al. 1996a) where the values of some dominating parameters were estimated and the dependence of the resulting flow field on these values was not checked. Received 22 April 1996 / Accepted 5 January 1997     

Kinking of a crack emanating from the free surface of a beam under pure bending

A perturbation technique developed by Karihaloo et al. is employed to obtain the stress intensity factors at the tip of a kinking crack that emanates from the free surface of a beam under pure bending. Under the condition that the kink extends in the direction of vanishing K₁₁ the crack path is obtained as well as a path stability condition. From conditions on K₁ a material parameter r^* akin to that of Ramulu and Kobayashi's r_c is obtained. By analysis of the slope of the kinking crack a stability condition is obtained corroborating the stability condition from consideration of vanishing K₁₁. It is shown that for a beam in pure bending the nonsingular remote stress term T must be greater than some positive critical value for kinking to occur confirming the results of Sayir and Schindler.     

Communication: folding of glycosylated proteins under confinement

Conjugating flexible polymers (such as oligosaccharides) to proteins or confining a protein in a restricted volume often increases protein thermal stability. In this communication, we investigate the interplay between conjugation and confinement which is not trivial as the magnitude and the mechanism of stabilization are different in each instance. Using coarse-grained computational approach the folding biophysics is studied when the protein is placed in a sphere of variable radius and is conjugated to 0-6 mono- or penta-saccharides. We observe a synergistic effect on thermal stability when short oligosaccharides are attached and the modified protein is confined in a small cage. However, when large oligosaccharides are added, a conflict between confinement and glycosylation arises as the stabilizing effect of the cage is dramatically reduced and it is almost impossible to further stabilize the protein beyond the mild stabilization induced by the sugars.     

Ab initio calculation of the lowest ionization potential and transition energies of methane

The lowest ionization potential and transition energies of methane are calculated by a second-order perturbation expansion, using a limited basis of gaussian-type orbitals. An attempt is made to rationalize the choice of basis atomic orbitals. This procedure yields 13·8 eV for the first ionization potential and 10·4 eV for the lowest allowed transition provided a diffuse molecular orbital is added to describe the excited state (the experimental values are 13·6 and 9·7 eV). These two values include contributions of -1·0 and -0·70 eV, respectively, from an approximate optimization of the basis atomic orbitals and of +0·50 and +0·25 eV from electron correlation.     

Calculation of the nuclear magnetic shielding of 29Si, 31P, 33S and 35Cl using a pseudo-potential method

The nuclear magnetic shielding of ²⁹Si, ³¹P, ³³S and ³⁵Cl in SiH₄, PH₃, SH₂ and ClH has been computed. The inner shells of the heavy atom are not introduced in the calculation for the molecule. Their effect on the valence shell is represented by a pseudo-potential. The agreement with available theoretical and experimental values is satisfactory.