Performance of machine-learning scoring functions in structure-based virtual screening

Classical scoring functions have reached a plateau in their performance in virtual screening and binding affinity prediction. Recently, machine-learning scoring functions trained on protein-ligand complexes have shown great promise in small tailored studies. They have also raised controversy, specifically concerning model overfitting and applicability to novel targets. Here we provide a new ready-to-use scoring function (RF-Score-VS) trained on 15 426 active and 893 897 inactive molecules docked to a set of 102 targets. We use the full DUD-E data sets along with three docking tools, five classical and three machine-learning scoring functions for model building and performance assessment. Our results show RF-Score-VS can substantially improve virtual screening performance: RF-Score-VS top 1% provides 55.6% hit rate, whereas that of Vina only 16.2% (for smaller percent the difference is even more encouraging: RF-Score-VS top 0.1% achieves 88.6% hit rate for 27.5% using Vina). In addition, RF-Score-VS provides much better prediction of measured binding affinity than Vina (Pearson correlation of 0.56 and -0.18, respectively). Lastly, we test RF-Score-VS on an independent test set from the DEKOIS benchmark and observed comparable results. We provide full data sets to facilitate further research in this area (http://github.com/oddt/rfscorevs) as well as ready-to-use RF-Score-VS (http://github.com/oddt/rfscorevs_binary)

Laboratory station to two phase flows investigations in porous media

Treścią artykułu jest ocena stanowiska laboratoryjnego do badania przepływów wielofazowych w ośrodkach porowatych, które powstało w ramach Projektu Badawczego nr 8T12A04020 finansowanego przez KBN oraz badań statutowych i własnych realizowanych w Zakładzie Gazownictwa Ziemnego Wydziału Wiertnictwa Nafty i Gazu AGH w Krakowie. Stanowisko badawcze umożliwia prowadzenie badań wzajemnego wypierania dwóch płynów w układach: gaz -gaz i gaz - ciecz. Badania realizowano z użyciem trzech gazów - metanu, sztucznego powietrza, azotu, oraz wody. Powietrze używane było głównie do prowadzenia badań testowych aparatury w zakresie jej szczelności oraz pomiaru przepuszczalności ośrodka porowatego. Na skonstruowanym stanowisku wykonano pomiary w układzie: gaz - gaz i woda - gaz. Badania wypierania się gazów o różnych własnościach termodynamicznych polegały na pomiarze koncentracji gazu wypierającego na wyjściu z komory pomiarowej. Na tej podstawie ustalono zależności pomiędzy wzajemnym nasyceniem oboma gazami a czasem przetłaczania. Celem tych badań było ustalenie stopnia wzajemnego mieszania się metanu i azotu w ośrodku porowatym Badanie wypierania się układu woda - gaz polegało na pomiarze zawartości wody w sztucznym złożu przy użyciu aparatury mikrofalowej. Na podstawie tych badań próbowano ustalić kryteria rozmywania się konturu woda - gaz. Przeprowadzone badania w pełni potwierdziły przydatność zbudowanego stanowiska laboratoryjnego. Badania wzajemnego wypierania się różnych płynów będą wykonywane w kolejnych latachContents of this paper is the valuation of laboratory station for two phase flows in porous media. This station was contracted at The Gas Department of Drilling, Oil and Gas Faculty AGH University of Science and Technology in Kraków funded by KBN (Project 8T12A04020). This laboratory station enable to carry out the laboratory investigations of two phase flows (gas - gas and water - gas) in porous media. The investigation of mutual gas displacement and the measurement of their concentration at the output of measure chamber. The goal of that investigations it was to determine of methane - nitrogen mixing degree in porous media. The investigation of mutual gas - water displacement relay on the measurement of water concentration in reservoir by means of microwave apparatus. On the base of this investigations authors test to fix criteria of gas - water contour stability. All carried out investigations fixed usefulness of constracted laboratory station. The investigations will be continued in next year

Effect of the axial ligand on substrate sulfoxidation mediated by iron(IV)-oxo porphyrin cation radical oxidants

Cytochromes P 450 catalyze a range of different oxygen-transfer processes including aliphatic and aromatic hydroxylation, epoxidation, and sulfoxidation reactions. Herein, we have investigated substrate sulfoxidation mediated by models of P 450 enzymes as well as by biomimetic oxidants using density functional-theory methods and we have rationalized the sulfoxidation reaction barriers and rate constants. We carried out two sets of calculations: first, we calculated the sulfoxidation by an iron(IV)–oxo porphyrin cation radical oxidant [Fe<SUP>IV</SUP>=O(Por<SUP>+.</SUP>)SH] that mimics the active site of cytochrome P 450 enzymes with a range of different substrates, and second, we studied one substrate (dimethyl sulfide) with a selection of different iron(IV)–oxo porphyrin cation radical oxidants [Fe<SUP>IV</SUP>=O(Por<SUP>+.</SUP>)L] with varying axial ligands L. The study presented herein shows that the barrier height for substrate sulfoxidation correlates linearly with the ionization potential of the substrate, thus reflecting the electron-transfer processes in the rate-determining step of the reaction. Furthermore, the axial ligand of the oxidant influences the pK<SUB>a</SUB> value of the iron(IV)–oxo group, and, as a consequence, the bond dissociation energy (BDE<SUB>OH</SUB>) value correlates with the barrier height for the reverse sulfoxidation reaction. These studies have generalized substrate-sulfoxidation reactions and have shown how they fundamentally compare with substrate hydroxylation and epoxidation reactions