Blind prediction of host–guest binding affinities: a new SAMPL3 challenge

The computational prediction of protein-ligand binding affinities is of central interest in early-stage drug-discovery, and there is a widely recognized need for improved methods. Low molecular weight receptors and their ligands--i.e., host-guest systems--represent valuable test-beds for such affinity prediction methods, because their small size makes for fast calculations and relatively facile numerical convergence. The SAMPL3 community exercise included the first ever blind prediction challenge for host-guest binding affinities, through the incorporation of 11 new host-guest complexes. Ten participating research groups addressed this challenge with a variety of approaches. Statistical assessment indicates that, although most methods performed well at predicting some general trends in binding affinity, overall accuracy was not high, as all the methods suffered from either poor correlation or high RMS errors or both. There was no clear advantage in using explicit versus implicit solvent models, any particular force field, or any particular approach to conformational sampling. In a few cases, predictions using very similar energy models but different sampling and/or free-energy methods resulted in significantly different results. The protonation states of one host and some guest molecules emerged as key uncertainties beyond the choice of computational approach. The present results have implications for methods development and future blind prediction exercises.     

Comparing topological charge definitions using topology fixing actions

We investigate both the hyperbolic action and the determinant ratio action designed to fix the topological charge on the lattice. We show to what extent topology is fixed depending on the parameters of these actions, keeping the physical situation fixed. At the same time the agreement between different definitions of topological charge --the field theoretic and the index definition-- is directly correlated to the degree topology is fixed. Moreover, it turns out that the two definitions agree very well. We also study finite-volume effects arising in the static potential and related quantities due to topology fixing.     

A CLIMATOLOGY OF SUNBURNING ULTRAVIOLET RADIATION

Abstract— Data are presented from 14 sites where continuous measurements of the sun's shortest ultraviolet radiation reaching the earth's surface have been made for four or more years. Average daily dose per month and its variability from year to year is shown for each station. Some of the many influences affecting these measurements can be discerned by station intercomparisons. No consistent long term change in solar UV-B radiation reaching the ground is evident.     

UV doses of young adults

Since 1986, people have been informed that they get about 80% of their lifetime ultraviolet (UV) dose by the age of 18. This belief originated from the mathematical conclusion that diligent use of sunscreens (sun protection factor 15 or higher) during the first 18 years of life would reduce the lifetime incidence of nonmelanoma skin cancers by 78%. These data were misconstrued to mean that individuals also got about 80% of their lifetime dose of UV by the age of 18 (linear relationship). However, these calculations were based on the incidence of nonmelanoma skin cancers being related to the square of the UV dose. Careful analysis of UV exposure data shows that Americans actually get less than 25% of their lifetime UV dose by the age of 18. This finding also appears to be true worldwide because Australia, UK and The Netherlands report a similar UV exposure pattern. UV-initiated damage early in life can be promoted by subsequent exposures to progress into tumors later in life. For example, the nonmelanoma skin cancer, squamous cell carcinoma, is dependent on the cumulative UV dose. Thus, a better educational approach for reducing skin cancers would be to instruct fair-skinned individuals to protect themselves throughout their lives from being exposed to too much UV radiation.     

Twisted mass quarks and the phase structure of lattice QCD

The phase structure of zero temperature twisted mass lattice QCD is investigated. We find strong metastabilities in the plaquette observable in correspondence of which the untwisted quark mass assumes positive or negative values. We provide interpretations of this phenomenon in terms of chiral symmetry breaking and the effective potential model of Sharpe and Singleton.Received: 24 August 2004, Revised: 29 October 2004, Published online: 25 January 2005     

Two-dimensional melting far from equilibrium in a granular monolayer

We report an experimental investigation of the transition from a hexagonally ordered solid phase to a disordered liquid in a monolayer of vibrated spheres. The transition occurs as the intensity of the vibration amplitude is increased. Measurements of the density of dislocations and the positional and orientational correlation functions show evidence for a dislocation-mediated continuous transition from a solid phase with long-range order to a liquid with only short-range order. The results show a strong similarity to simulations of melting of hard disks in equilibrium, despite the fact that the granular monolayer is far from equilibrium due to the effects of interparticle dissipation and the vibrational forcing.