The effect of tightly-bound water molecules on scaffold diversity in computer-aided de novo ligand design of CDK2 inhibitors

We have determined the effects that tightly bound water molecules have on the de novo design of cyclin-dependent kinase-2 (CDK2) ligands. In particular, we have analyzed the impact of a specific structural water molecule on the chemical diversity and binding mode of ligands generated through a de novo structure-based ligand generation method in the binding site of CDK2. The tightly bound water molecule modifies the size and shape of the binding site and we have found that it also imposed constraints on the observed binding modes of the generated ligands. This in turn had the indirect effect of reducing the chemical diversity of the underlying molecular scaffolds that were able to bind to the enzyme satisfactorily

Triply interlocked covalent organic cages

Interlocked molecules comprise two or more separate components that are joined by ‘mechanical’ rather than covalent bonds. In other words, these molecular assemblies cannot be dissociated without the cleavage of one or more chemical bonds. Although recent progress has enabled the preparation of such topologies through coordination or templating interactions, three-dimensional interlocked covalent architectures remain difficult to prepare. Here, we present a template-free one-pot synthesis of triply interlocked organic cages. These 20-component dimers consist of two tetrahedral monomeric cages each built from four nodes and six linkers. The monomers exhibit axial chirality, which is recognized by their partner cage during the template-free interlocking assembly process. The dimeric cages also include two well-defined cavities per assembly, which for one of the systems studied led to the formation of a supramolecular host–guest chain. These interlocked organic molecules may prove useful as part of a toolkit for the modular construction of complex porous solids and other supramolecular assemblies

Does Culture Affect Divorce? Evidence From European Immigrants in the United States

This article explores the role of culture in determining divorce by examining country-of-origin differences in divorce rates of immigrants in the United States. Because childhood-arriving immigrants are all exposed to a common set of U.S. laws and institutions, we interpret relationships between their divorce tendencies and home-country divorce rates as evidence of the effect of culture. Our results are robust to controlling for several home-country variables, including average church attendance and gross domestic product (GDP). Moreover, specifications with country-of-origin fixed effects suggest that immigrants from countries with low divorce rates are especially less likely to be divorced if they reside among a large number of coethnics. Supplemental analyses indicate that divorce culture has a stronger impact on the divorce decisions of females than of males, pointing to a potentially gendered nature of divorce taboos