Similarity search profiles as a diagnostic tool for the analysis of virtual screening calculations

An analysis method termed similarity search profiling has been developed to evaluate fingerprint-based virtual screening calculations. The analysis is based on systematic similarity search calculations using multiple template compounds over the entire value range of a similarity coefficient. In graphical representations, numbers of correctly identified hits and other detected database compounds are separately monitored. The resulting profiles make it possible to determine whether a virtual screening trial can in principle succeed for a given compound class, search tool, similarity metric, and selection criterion. As a test case, we have analyzed virtual screening calculations using a recently designed fingerprint on 23 different biological activity classes in a compound source database containing approximately 1.3 million molecules. Based on our predefined selection criteria, we found that virtual screening analysis was successful for 19 of 23 compound classes. Profile analysis also makes it possible to determine compound class-specific similarity threshold values for similarity searching.     

Combinatorial preferences affect molecular similarity/diversity calculations using binary fingerprints and Tanimoto coefficients

A combinatorial method was developed to calculate complete distributions of the Tanimoto coefficient (Tc) for binary fingerprint (FP) representations of specified length, regardless of the chemical parameters they reflect. Theoretical Tc distributions were calculated for FPs consisting of up to 67 bit positions which revealed significant statistical preferences of certain Tc values. Calculation of Tc distributions in a large compound database using different FPs mirrored the effects identified by our general analysis. On the basis of these findings, an average Tc is biased by statistically preferred values.     

Phonon-induced Rabi-frequency renormalization of optically driven single InGaAs/GaAs quantum dots

We study optically driven Rabi rotations of a quantum dot exciton transition between 5 and 50 K, and for pulse areas of up to 14π. In a high driving field regime, the decay of the Rabi rotations is nonmonotonic, and the period decreases with pulse area and increases with temperature. By comparing the experiments to a weak-coupling model of the exciton-phonon interaction, we demonstrate that the observed renormalization of the Rabi frequency is induced by fluctuations in the bath of longitudinal acoustic phonons, an effect that is a phonon analogy of the Lamb shift.