What do we know and when do we know it?

Two essential aspects of virtual screening are considered: experimental design and performance metrics. In the design of any retrospective virtual screen, choices have to be made as to the purpose of the exercise. Is the goal to compare methods? Is the interest in a particular type of target or all targets? Are we simulating a ‘real-world’ setting, or teasing out distinguishing features of a method? What are the confidence limits for the results? What should be reported in a publication? In particular, what criteria should be used to decide between different performance metrics? Comparing the field of molecular modeling to other endeavors, such as medical statistics, criminology, or computer hardware evaluation indicates some clear directions. Taken together these suggest the modeling field has a long way to go to provide effective assessment of its approaches, either to itself or to a broader audience, but that there are no technical reasons why progress cannot be made.     

Molecular shape and electrostatics in the encoding of relevant chemical information

We propose a molecule's chemistry can be hidden by representations of its shape and electrostatic field while retaining crucial, pharmaceutically relevant, information. Necessary, but not sufficient, to this proposition are the importance of shape and electrostatics to activity, the facility to easily represent, store and compare field properties, and knowledge of the density of possible drug-like molecules within a given radius of physical similarity. We provide methods and evidence to support the conclusion that a useful encoding is practical and propose tests for falsification.     

Andreev probe of persistent current states in superconducting quantum circuits

Using the extraordinary sensitivity of Andreev interferometers to the superconducting phase difference associated with currents, we measure the persistent current quantum states in superconducting loops interrupted by Josephson junctions. Straightforward electrical resistance measurements of the interferometers give a continuous readout of the states, allowing us to construct the energy spectrum of the quantum circuit. The probe is estimated to be more precise and faster than previous methods, and can measure the local phase difference in a wide range of superconducting circuits.     

Model studies on the systematics and interpolation of Franck-Condon factor arrays

A simple harmonic oscillator approximation is used to derive approximate algebraic expressions for low vibrational quantum number Franck-Condon factors for band systems for which molecular data are sparse. These simple expressions involve a transition parameter u which is characteristic of the electronic transition involved. The expressions provide Franck-Condon factors which agree quite well with RKR values when these are available. The formulae are used to explain quantitatively the dependence on u of the systematic properties of Franck-Condon factor arrays and to provide a method for their interpolation. The formulae are also used to describe quantitatively the dependence on u of the gross appearance of molecular band systems in emission and absorption.     

Inelastic p-He scattering at 141 MeV

Inelastic p-⁴He scattering at 141±2 MeV has been investigated with a high-pressure cloud chamber filled with helium. Results are presented for the total cross sections of each reaction channel and the neutron spectra for the p(⁴He, pn)³He reaction.     

A <Emphasis Type="Italic">k</Emphasis>-nearest neighbor classification of hERG K<Superscript>+</Superscript> channel blockers

A series of 172 molecular structures that block the hERG K⁺ channel were used to develop a classification model where, initially, eight types of PaDEL fingerprints were used for k-nearest neighbor model development. A consensus model constructed using Extended-CDK, PubChem and Substructure count fingerprint-based models was found to be a robust predictor of hERG activity. This consensus model demonstrated sensitivity and specificity values of 0.78 and 0.61 for the internal dataset compounds and 0.63 and 0.54 for the external (PubChem) dataset compounds, respectively. This model has identified the highest number of true positives (i.e. 140) from the PubChem dataset so far, as compared to other published models, and can potentially serve as a basis for the prediction of hERG active compounds. Validating this model against FDA-withdrawn substances indicated that it may even be useful for differentiating between mechanisms underlying QT prolongation.