Predicting protein-ligand affinity with a random matrix framework

Rapid determination of whether a candidate compound will bind to a particular target receptor remains a stumbling block in drug discovery. We use an approach inspired by random matrix theory to decompose the known ligand set of a target in terms of orthogonal "signals" of salient chemical features, and distinguish these from the much larger set of ligand chemical features that are not relevant for binding to that particular target receptor. After removing the noise caused by finite sampling, we show that the similarity of an unknown ligand to the remaining, cleaned chemical features is a robust predictor of ligand-target affinity, performing as well or better than any algorithm in the published literature. We interpret our algorithm as deriving a model for the binding energy between a target receptor and the set of known ligands, where the underlying binding energy model is related to the classic Ising model in statistical physics.This research was funded by a grant from Roche Pharmaceuticals. A.A.L. acknowledges the support of a Fulbright Fellowship. L.J.C. was supported by a Next Generation Fellowship, and a Marie Curie Career Integration Grant (Evo-Couplings, Grant 631609). M.P.B. is an investigator of the Simons Foundation, and also acknowledges support from the National Science Foundation through DMS-1411694

The Dimensional Recurrence and Analyticity Method for Multicomponent Master Integrals: Using Unitarity Cuts to Construct Homogeneous Solutions

We consider the application of the DRA method to the case of several master integrals in a given sector. We establish a connection between the homogeneous part of dimensional recurrence and maximal unitarity cuts of the corresponding integrals: a maximally cut master integral appears to be a solution of the homogeneous part of the dimensional recurrence relation. This observation allows us to make a necessary step of the DRA method, the construction of the general solution of the homogeneous equation, which, in this case, is a coupled system of difference equations.Comment: 17 pages, 2 figure

Terrestrial exposure of a fresh Martian meteorite causes rapid changes in hydrogen isotopes and water concentrations

Determining the hydrogen isotopic compositions and H2O contents of meteorites and their components is important for addressing key cosmochemical questions about the abundance and source(s) of water in planetary bodies. However, deconvolving the effects of terrestrial contamination from the indigenous hydrogen isotopic compositions of these extraterrestrial materials is not trivial, because chondrites and some achondrites show only small deviations from terrestrial values such that even minor contamination can mask the indigenous values. Here we assess the effects of terrestrial weathering and contamination on the hydrogen isotope ratios and H2O contents of meteoritic minerals through monitored terrestrial weathering of Tissint, a recent Martian fall. Our findings reveal the rapidity with which this weathering affects nominally anhydrous phases in extraterrestrial materials, which illustrates the necessity of sampling the interiors of even relatively fresh meteorite falls and underlines the importance of sample return missions

The localization of multiple cathepsin mRNAs in the seminiferous epithelium by in situ hybridization is consistent with their role in germ cell (GC) migration

Abstract no. 707published_or_final_versio