Molecular dynamics analysis to evaluate docking pose prediction.

The accurate prediction of a ligand-protein complex structure is important for computer-assisted drug development. Although many docking methods have been developed over the last three decades, the success of binding structure prediction remains greatly limited. The purpose of this study was to demonstrate the usefulness of molecular dynamics (MD) simulation in assessing a docking pose predicted using a docking program. If the predicted pose is not unstable in an aqueous environment, MD simulation equilibrates the system and removes the ligand from the predicted position. Here we investigated two proteins that are important potential therapeutic targets: ß2 adrenergic receptor (ß2AR) and PR-Set7. While ß2AR is rigid and its ligands are very similar to the template ligand (carazolol), PR-Set7 is very flexible and its ligands vary greatly from the template ligand (histone H4 tail peptide). On an empirical basis, we usually expect that the docking prediction is accurate when the protein is rigid and its ligands are similar to the template ligand. The MD analyses in this study clearly suggested such a tendency. Furthermore, we discuss the possibility that the MD simulation can predict the binding pose of a ligand.

Effect of long-term combined application of organic and inorganic fertilizers on soil nematode communities within aggregates.

A long-term fertilization experiment was conducted to examine the effects of different fertilization practices on nematode community composition within aggregates in a wheat-maize rotation system. The study was a randomized complete block design with three replicates. The experiment involved the following four treatments: no fertilizer, inorganic N, P and K fertilizer (NPK), NPK plus manure (NPKM) and NPK plus maize straw (NPKS). Soil samples were taken at 0-20 cm depth during the wheat harvest stage. Based on our results, NPKS contributed to soil aggregation and moisture retention, with a positive effect on soil total nitrogen accumulation, particularly within small macroaggregates (0.25-1 mm) and microaggregates (<0.25 mm). The C/N ratio was correlated to the distribution of the soil nematode community. Both manure application and straw incorporation increased the nematode functional metabolic footprints within all aggregates. Additionally, the functional metabolic footprints decreased with a decline in aggregate size. The accumulation of total nitrogen within <1 mm aggregates under NPKS might play a key role in maintaining the survival of soil nematodes. In our study, both crop straw incorporation and inorganic fertilizer application effectively improved soil physicochemical properties and were also beneficial for nematode survival within small aggregate size fractions.