Change In Solvent-accessible Area Research Articles

Can Dispersion Forces Govern Aromatic Stacking in an Organic Solvent?

Experimental support for the dominance of van der Waals dispersion forces in aromatic stacking interactions occurring in organic solution is surprisingly limited. The size-dependence of aromatic stacking in an organic solvent was examined. The interaction energy was found to vary by about 7.5 kJ mol(-1) on going from a phenyl-phenyl to an anthracene-pyrene stack. Strikingly, the experimental data were highly correlated with dispersion energies determined using symmetry-adapted perturbation theory (SAPT), while the induction, exchange, electrostatic, and solvation energy components correlated poorly. Both the experimental data and the SAPT-dispersion energies gave high-quality correlations with the change in solvent accessible area upon complexation. Thus, the size-dependence of aromatic stacking interactions is consistent with the dominance of van der Waals dispersion forces even in the presence of a competing polarizable solvent.

Can Dispersion Forces Govern Aromatic Stacking in an Organic Solvent?

AbstractExperimental support for the dominance of van der Waals dispersion forces in aromatic stacking interactions occurring in organic solution is surprisingly limited. The size‐dependence of aromatic stacking in an organic solvent was examined. The interaction energy was found to vary by about 7.5 kJ mol−1 on going from a phenyl–phenyl to an anthracene–pyrene stack. Strikingly, the experimental data were highly correlated with dispersion energies determined using symmetry‐adapted perturbation theory (SAPT), while the induction, exchange, electrostatic, and solvation energy components correlated poorly. Both the experimental data and the SAPT‐dispersion energies gave high‐quality correlations with the change in solvent accessible area upon complexation. Thus, the size‐dependence of aromatic stacking interactions is consistent with the dominance of van der Waals dispersion forces even in the presence of a competing polarizable solvent.

A thermodynamic analysis of fibrillar polymorphism

We explore the thermodynamic properties of three different fibrils of the peptide hormone glucagon, formed under different salt conditions (glycine, sulfate and NaCl, respectively), and differing considerably in compactness. The three fibrils display a large variation in the specific heat capacity Δ C p determined by isothermal titration calorimetry. Sulfate fibrils show a negative Δ C p expected from a folding reaction, while the Δ C p for glycine fibrils is essentially zero. NaCl fibrils, which are less stable than the other fibrils, have a large and positive ∆ C p. The predicted change in solvent accessible area is not a useful predictor of fibrillar Δ C p unlike the case for globular proteins. We speculate that strong backbone interactions may lead to the unfavorable burial of polar side residues, water and/or charged groups which all can have major influence on the change in ∆ C p. These results highlight differences in the driving forces of native folding and fibril formation.

X-ray crystallographic analysis of inhibition of endothiapepsin by cyclohexyl renin inhibitors.

The crystal structures of endothiapepsin, a fungal aspartic proteinase (EC 3.4.23.6), cocrystallized with two oligopeptide renin inhibitors, PD125967 and PD125754, have been determined at 2.0-A resolution and refined to R-factors of 0.143 and 0.153, respectively. These inhibitors, which are of the hydroxyethylene and statine types, respectively, possess a cyclohexylalanine side chain at P1 and have interesting functionalities at the P3 position which, until now, have not been subjected to crystallographic analysis. PD125967 has a bis(1-naphthylmethyl)acetyl residue at P3, and PD125754 possesses a hydroxyethylene analogue of the P3-P2 peptide bond for proteolytic stability. The structures reveal that the S3 pocket accommodates one naphthyl ring with conformational changes of the Asp 77 and Asp 114 side chains, the other naphthyl group residing in the S4 region. The P3-P2 hydroxyethylene analogue of PD125754 forms a hydrogen bond with the NH of Thr 219, thereby making the same interaction with the enzyme as the equivalent peptide groups of all inhibitors studied so far. The absence of side chains at the P2 and P1' positions of this inhibitor allows water molecules to occupy the respective pockets in the complex. The relative potencies of PD125967 and PD125754 for endothiapepsin are consistent with the changes in solvent-accessible area which take place on inhibitor binding.