rDock: A Fast, Versatile and Open Source Program for Docking Ligands to Proteins and Nucleic Acids

Identification of chemical compounds with specific biological activities is an important step in both chemical biology and drug discovery. When the structure of the intended target is available, one approach is to use molecular docking programs to assess the chemical complementarity of small molecules with the target; such calculations provide a qualitative measure of affinity that can be used in virtual screening (VS) to rank order a list of compounds according to their potential to be active. rDock is a molecular docking program developed at Vernalis for high-throughput VS (HTVS) applications. Evolved from RiboDock, the program can be used against proteins and nucleic acids, is designed to be computationally very efficient and allows the user to incorporate additional constraints and information as a bias to guide docking. This article provides an overview of the program structure and features and compares rDock to two reference programs, AutoDock Vina (open source) and Schrodinger's Glide (commercial). In terms of computational speed for VS, rDock is faster than Vina and comparable to Glide. For binding mode prediction, rDock and Vina are superior to Glide. The VS performance of rDock is significantly better than Vina, but inferior to Glide for most systems unless pharmacophore constraints are used; in that case rDock and Glide are of equal performance. The program is released under the Lesser General Public License and is freely available for download, together with the manuals, example files and the complete test sets, at http://rdock.sourceforge.net/

A tractable consideration set structure for network revenue management

Models incorporating more realistic models of customer behavior, as customers choosing from an offerset, have recently become popular in assortment optimization and revenue management. The dynamicprogram for these models is intractable and approximated by a deterministic linear program called theCDLP which has an exponential number of columns. When there are products that are being consideredfor purchase by more than one customer segment, CDLP is difficult to solve since column generationis known to be NP-hard. However, recent research indicates that a formulation based on segments withcuts imposing consistency (SDCP+) is tractable and approximates the CDLP value very closely. In thispaper we investigate the structure of the consideration sets that make the two formulations exactly equal.We show that if the segment consideration sets follow a tree structure, CDLP = SDCP+. We give acounterexample to show that cycles can induce a gap between the CDLP and the SDCP+ relaxation.We derive two classes of valid inequalities called flow and synchronization inequalities to further improve(SDCP+), based on cycles in the consideration set structure. We give a numeric study showing theperformance of these cycle-based cuts.

Progress in the Spanish National Barley Breeding Program

The Spanish Barley Breeding Program is carried out by four public research organizations, located at the most representative barley growing regions of Spain. The aim of this study is to evaluate the program retrospectively, attending to: i) the progress achieved in grain yield, and ii) the extent and impact of genotype-by-environment interaction of grain yield. Grain yields and flowering dates of 349 advanced lines in generations F8, F9 and F10, plus checks, tested at 163 trials over 11 years were analized. The locations are in the provinces of Albacete, Lleida, Valladolid and Zaragoza. The data are highly unbalanced because the lines stayed at the program for a maximum of three years. Progress was estimated using relative grain yield and mixed models (REML) to homogenize the results among years and locations. There was evident progress in the program over the period studied, with increasing relative yields in each generation, and with advanced lines surpassing the checks in the last two generations, although the rate of progress was uneven across locations. The genetic gain was greater from F8 to F9 than from F9 to F10. The largest non-purely environmental component of variance was genotype-by-location-by-year, meaning that the genotype-by-location pattern was highly unpredictable. The relationship between yield and flowering time overall was weak in the locations under study at this advanced stage of the program. The program can be continued with the same structure, although measures should be taken to explore the causes of slower progress at certain locations.