Bayesian analysis of isothermal titration calorimetry for binding thermodynamics.

Isothermal titration calorimetry (ITC) is the only technique able to determine both the enthalpy and entropy of noncovalent association in a single experiment. The standard data analysis method based on nonlinear regression, however, provides unrealistically small uncertainty estimates due to its neglect of dominant sources of error. Here, we present a Bayesian framework for sampling from the posterior distribution of all thermodynamic parameters and other quantities of interest from one or more ITC experiments, allowing uncertainties and correlations to be quantitatively assessed.

SWEETLEAD: an in silico database of approved drugs, regulated chemicals, and herbal isolates for computer-aided drug discovery.

In the face of drastically rising drug discovery costs, strategies promising to reduce development timelines and expenditures are being pursued. Computer-aided virtual screening and repurposing approved drugs are two such strategies that have shown recent success. Herein, we report the creation of a highly-curated in silico database of chemical structures representing approved drugs, chemical isolates from traditional medicinal herbs, and regulated chemicals, termed the SWEETLEAD database.

Marked difference in saxitoxin and tetrodotoxin affinity for the human nociceptive voltage-gated sodium channel (Nav1.7) [corrected].

Human nociceptive voltage-gated sodium channel (Na(v)1.7), a target of significant interest for the development of antinociceptive agents, is blocked by low nanomolar concentrations of (-)-tetrodotoxin(TTX) but not (+)-saxitoxin (STX) and (+)-gonyautoxin-III (GTX-III). These findings question the long-accepted view that the 1.

Design of β-amyloid aggregation inhibitors from a predicted structural motif.

Drug design studies targeting one of the primary toxic agents in Alzheimer's disease, soluble oligomers of amyloid β-protein (Aβ), have been complicated by the rapid, heterogeneous aggregation of Aβ and the resulting difficulty to structurally characterize the peptide. To address this, we have developed [Nle(35), D-Pro(37)]Aβ(42), a substituted peptide inspired from molecular dynamics simulations which forms structures stable enough to be analyzed by NMR. We report herein that [Nle(35), D-Pro(37)]Aβ(42) stabilizes the trimer and prevents mature fibril and β-sheet formation.