Influence of Ground Motion Variability on Design Spectra in Areas of Low to Moderate Seismicity

This paper examines the sensitivity of uniform hazard response spectra to the variability of the ground motion attenuation in areas of low to moderate seismicity. The variabilities of a number of published attenuation relationships are examined. Many of these relationships show that the standard deviation tends to increase as the natural period increases and some show a tendency for the standard deviation to reduce as the earthquake magnitude increases. These published works tend to be derived from earthquake data for areas of high seismicity and therefore the paper includes a critical review of what values of standard deviation are appropriate for regions of low to moderate seismicity

A Remote Arene-Binding Site on Prostate Specific Membrane Antigen Revealed by Antibody-Recruiting Small Molecules

Prostate specific membrane antigen (PSMA) is a membrane-bound glutamate carboxypeptidase overexpressed in many forms of prostate cancer. Our laboratory has recently disclosed a class of small molecules, called ARM-Ps (antibody-recruiting molecule targeting prostate cancer) that are capable of enhancing antibody-mediated immune recognition of prostate cancer cells. Interestingly, during the course of these studies, we found ARM-Ps to exhibit extraordinarily high potencies toward PSMA, compared to previously reported inhibitors. Here, we report in-depth biochemical, crystallographic, and computational investigations which elucidate the origin of the observed affinity enhancement. These studies reveal a previously unreported arene-binding site on PSMA, which we believe participates in an aromatic stacking interaction with ARMs. Although this site is composed of only a few amino acid residues, it drastically enhances small molecule binding affinity. These results provide critical insights into the design of PSMA-targeted small molecules for prostate cancer diagnosis and treatment; more broadly, the presence of similar arene-binding sites throughout the proteome could prove widely enabling in the optimization of small-molecule–protein interactions

Structural and functional properties of Bauhinia forficata lectin (BfL)

Univ Fed São Paulo, São Paulo, BrazilUniv Fed São Paulo, São Paulo, BrazilWeb of Scienc