The statistical-thermodynamic basis for computation of binding affinities: a critical review

Although the statistical thermodynamics of noncovalent binding has been considered in a number of theoretical papers, few methods of computing binding affinities are derived explicitly from this underlying theory. This has contributed to uncertainty and controversy in certain areas. This article therefore reviews and extends the connections of some important computational methods with the underlying statistical thermodynamics. A derivation of the standard free energy of binding forms the basis of this review. This derivation should be useful in formulating novel computational methods for predicting binding affinities. It also permits several important points to be established. For example, it is found that the double-annihilation method of computing binding energy does not yield the standard free energy of binding, but can be modified to yield this quantity. The derivation also makes it possible to define clearly the changes in translational, rotational, configurational, and solvent entropy upon binding. It is argued that molecular mass has a negligible effect upon the standard free energy of binding for biomolecular systems, and that the cratic entropy defined by Gurney is not a useful concept. In addition, the use of continuum models of the solvent in binding calculations is reviewed, and a formalism is presented for incorporating a limited number of solvent molecules explicitly

Southward expansion: The myth of the West in the promotion of Florida, 1876–1900

This article examines the ways in which promoters and developers of Florida, in the decades after Reconstruction, engaged with a popular myth of the West as a means of recasting and selling their state to prospective settlers in the North and Midwest. The myth envisaged a cherished region to the west where worthy Americans could migrate and achieve social and economic independence away from the crowded confines of the East, or Europe. According to state immigration agents, land-promoters and other booster writers, Florida, although a Southern ex-Confederate state, offered precisely these 'western' opportunities for those hard-working Northerners seeking land and an opening for agrarian prosperity. However, the myth, which posited that, in the west, an individual's labour and thrift were rewarded with social and economic improvement, meshed awkwardly with the contemporary emergence of Florida as a popular winter destination for wealthy tourists and invalids seeking leisure and healthfulness away from the North. Yet it also reflected and reinforced promotional notions of racial improvement which would occur with an influx of enterprising Anglo-Americans, who would effectively displace the state's large African American population. In Florida, the myth of the West supported the linked post-Reconstruction processes of state development and racial subjugation

Integrated Genomic Analysis of Diverse Induced Pluripotent Stem Cells from the Progenitor Cell Biology Consor tium

The rigorous characterization of distinct induced pluripotent stem cells (iPSC) derived from multiple reprogramming technologies, somatic sources, and donors is required to understand potential sources of variability and downstream potential. To achieve this goal, the Progenitor Cell Biology Consortium performed comprehensive experimental and genomic analyses of 58 iPSC from ten laboratories generated using a variety of reprogramming genes, vectors, and cells. Associated global molecular characterization studies identified functionally informative correlations in gene expression, DNA methylation, and/or copy-number variation among key developmental and oncogenic regulators as a result of donor, sex, line stability, reprogramming technology, and cell of origin. Furthermore, X-chromosome inactivation in PSC produced highly correlated differences in teratoma-lineage staining and regulator expression upon differentiation. All experimental results, and raw, processed, and metadata from these analyses, including powerful tools, are interactively accessible from a new online portal at https://www.synapse.org to serve as a reusable resource for the stem cell community