Prioritizing molecules for synthesis is a key role of computational methods within medicinal chemistry. Multiple tools exist for ranking molecules, from the cheap and popular molecular docking methods to more computationally expensive molecular‐dynamics (MD)‐based methods. It is often questioned whether the accuracy of the more rigorous methods justifies the higher computational cost and associated calculation time. Here, we compared the performance on ranking the binding of small molecules for seven scoring functions from five docking programs, one end‐point method (MM/GBSA), and two MD‐based free energy methods (PMX, FEP+). We investigated 16 pharmaceutically relevant targets with a total of 423 known binders. The performance of docking methods for ligand ranking was strongly system dependent. We observed that MD‐based methods predominantly outperformed docking algorithms and MM/GBSA calculations. Based on our results, we recommend the application of MD‐based free energy methods for prioritization of molecules for synthesis in lead optimization, whenever feasible.

IzvlečekUDK 556.114.5:627.8.034 Marko Breznik & Franci Steinman: Hidromehanizem in razslanitev obalnih kraških vodonosnikov: Teorija in primeriSomornica obalnih kraških vodonosnikov je neuporabna. Načini razslanjevanja so: prestrezanje sladke vode v kraški gmoti, izolacija vodonosnika in dvig gladine izvira za preprečenje vtoka morske vode, ter zmanjšanje črpanja sladke vode v sušnih obdobjih. Te načine pojasnjujejo štirje tipični primeri. Ključne besede: obalni kraški vodonosniki, razslanjevanje, načini, primeri. AbstractUDC 556.114.5:627.8.034 Marko Breznik & Franci Steinman: Hydromechanism and desalination of coastal karst aquifers: Theory and CasesBrackish water of coastal karst aquifers is useless. Desalination methods are: interception method to capture fresh water in karst massif, isolation and rise-spring-level methods to prevent sea water inflow and reduced pumping of fresh water in dry periods. Four typical cases explain these methods.

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Earthworms are key indicators of soil quality and health in vineyards, but research that considers different soil management systems, especially in Slovenian viticultural areas is scarce. In this investigation, the impact of different soil management practices such as permanent green cover, the use of herbicides in row and inter-row areas, use of straw mulch, and shallow soil tillage compared to meadow control for earthworm abundance, were assessed. The biomass and abundance of earthworms (m2) and distribution in various soil layers were quantified for three years. Monitoring and a survey covering 22 May 2014 to 5 October 2016 in seven different sampling dates, along with a soil profile at the depth from 0 to 60 cm, were carried out. Our results showed that the lowest mean abundance and biomass of earthworms in all sampling periods were registered along the herbicide strip (within the rows). The highest abundance was found in the straw mulch and permanent green cover treatments (higher than in the control). On the plots where the herbicide was applied to the complete inter-row area, the abundance of the earthworm community decreased from the beginning to the end of the monitoring period. In contrast, shallow tillage showed a similar trend of declining earthworm abundance, which could indicate a deterioration of soil biodiversity conditions. We concluded that different soil management practices greatly affect the soil’s environmental conditions (temperature and humidity), especially in the upper soil layer (up to 15 cm deep), which affects the abundance of the earthworm community. Our results demonstrated that these practices need to be adapted to the climate and weather conditions, and also to human impacts.