General and rigorous theory for equilibrium concentrations of uncomplexed species and 1 : 1, 1 : 2, 2 : 1, and 2 : 2 complexes of cyclodextrin (D) and surfactant has been developed and applied to evaluate the binding constants of these complexations from surface tension data of aqueous solutions of dodecyl maltoside (DM) with α-, β-, and γ-D, reported by Saeger and Muller-Fahrnow. The orders of the binding constants for 1 : 1 and 2 : 1 complexations of D and DM are α-D > β-D > γ-D. Those for 1 : 2 and 2 : 2 complexations are γ-D > β-D > α-D. These orders are explained on the basis of the goodness of fit of the dodecyl chain into the cyclodextrin cavity. Furthermore, the theory for the effects of D on the molar conductivity and the critical micelle concentration (cmc) of an ionic surfactant is modified by accounting for the change of these values with the surfactant concentration and applied to evaluate the binding constants for 1 : 1, 1 : 2, and 2 : 1 complexations of sodium dodecyl sulfate (SDS) and β-D from conductance and cmc data reported by Palepu and Reinsborough. Although there are several uncertainties in experimental data and their interpretations for the β-D-SDS system, the 1 : 1 complexation is predominant and its binding constant appears to be 5000 dm3 mol−1. Based on the present analysis, it is suggested that since a surfactant is a long and fine molecule, relative to aromatic compounds, its ternary and quaternary complexes with D’s as well as its binary complex should be taken into consideration.

From frontal chromatograms and derivatives of sodium taurocholate (TC) and taurodeoxycholate (TDC) on Sephadex G-10 columns in 0.154 M sodium chloride, monomer concentrations (Cl), weight and number average aggregation numbers excluding and including the monomer contribution, critical micelle concentrations (cmc's), and minimum multimerization concentrations have been determined as a function of the total concentration (C). Since the micellization of TC occurs rather noncritically, the cmc values obtained from the same centroid volume data depend on the data treatment. The definition of cmc, that cmc is the total concentration at the inflection on the C1 vs C curve, is applicable to TC and TDC as well as surfactants. The dimerization of TC and TDC has been proven by several pieces of chromatographic evidence, and their dimerization constants are determined independently from centroid volume and peak volume data. The stepwise aggregation constants are determined and are used to calculate micelle size distributions. Micelles of TC and TDC grow above the cmc more gradually than those of surfactants. This gradual growth is the main reason for inconsistencies in the literature of bile salt micellization. Since TDC is more hydrophobic than TC, the dimerization constant and aggregation numbers of TDC are larger than those of TC. This result supports the Small model for small micelles of bile salt.

The aggregation behavior of sodium taurocholate (TC) in deuterium oxide without salt was investigated by one-and two-dimensional NMR spectroscopy. Analysis of the concentration dependence of the chemical shift suggests that TC forms a dimer and a pentamer. The equilibrium constants of dimerization and pentamerization are close to those already determined by chromatography in the presence of 154 mM sodium chloride. The structure of the dimer is estimated from the NOESY and ROESY spectra of a 8 mM TC solution and molecular mechanics calculations. The inter-proton distances calculated from the molecular mechanics structure are consistent with the NOE and ROE intensities, whereas those calculated from the X-ray crystal structure (hydrogen-bonded structure) are inconsistent. The molecular mechanics structure is stabilized by hydrophobic interactions between the steroid nuclei and by reduced electrostatic repulsion between the sulfonate ions. The local structures of the pentamer are estimated on the basis of the ROESY spectrum of a 30 mM TC solution. The pentamer of TC is formed mainly by hydrophobic interactions. Thus, a novel NMR method in surfactant chemistry has provided the first step to resolve the 20-year debate about the structures of dimers and micelles of TC. This novel approach in surfactant chemistry will serve to estimate the structures of micelles of other natural and synthetic surfactants.

GM1 gangliosides form a microdomain with sphingomyeline (SM) and cholesterol (Chol) and are deeply involved in the aggregation of amyloid beta (Aβ) peptides on neural membranes. We performed molecular dynamics simulations on two kinds of lipid bilayers containing GM1 ganglioside: GM1/SM/Chol and GM1/POPC. Both 10 and 100 ns simulations and another set of 10 ns simulations with different initial lipid arrangement essentially showed the same computational results. GM1 molecules in the GM1/SM/Chol membrane were condensed, whereas those in GM1/POPC membrane scattered. That is, the formation of GM1 cluster was observed only on the GM1/SM/Chol mixed membrane. There appeared numerous hydrogen bonds among glycan portions of the GM1 clusters due to the condensation. A comparison in distribution of lipid molecules between the two kinds of membranes suggested that cholesterol had important roles to prevent the membrane from interdigitation and to stabilize other lipids for interacting with each other. This property of cholesterol promotes the formation of GM1 clusters.

Human immunodeficiency virus type 1 protease (HIV-1 PR) is one of the proteins that currently available anti-HIV-1 drugs target. Inhibitors of HIV-1 PR have become available, and they have lowered the rate of mortality from acquired immune deficiency syndrome (AIDS) in advanced countries. However, the rate of emergence of drug-resistant HIV-1 variants is quite high because of their short retroviral life cycle and their high mutation rate. Serious drug-resistant mutations against HIV-1 PR inhibitors (PIs) frequently appear at the active site of PR. Exceptionally, some other mutations such as L90M cause drug resistance, although these appear at nonactive sites. The mechanism of resistance due to nonactive site mutations is difficult to explain. In this study, we carried out computational simulations of L90M PR in complex with each of three kinds of inhibitors and one typical substrate, and we clarified the mechanism of resistance. The L90M mutation causes changes in interaction between the side chain atoms of the 90th residue and the main chain atoms of the 25th residue, and a slight dislocation of the 25th residue causes rotation of the side chain at the 84th residue. The rotation of the 84th residue leads to displacement of the inhibitor from the appropriate binding location, resulting in a collision with the flap or loop region. The difference in levels of resistance to the three inhibitors has been explained from energetic and structural viewpoints, which provides the suggestion for promising drugs keeping its efficacy even for the L90M mutant.