The long-term variation of the mean delta 13C-value of breath-CO2 of Europeans (base value -26%) was +/- 1% over a period of several months. However, the ingestion of products from corn, a C4-plant, caused remarkably higher shifts. In a fasted state and during rest a stability of the base value of +/- 0.3% could be attained for several hours. Longer fasting periods imply a shift of the CO2-delta-value due to the metabolism of body products. - By a change of the main energy source to corn products the delta 13C-base line could be shifted to -18% within one day. After this shift even the metabolism of products from C3-plants could be investigated. The degradation curve and the integral degradation of fats were largely dependent on the method of application, and the base value largely interfered with the results. The period of maximum disintegration for a naturally and uniformly labelled fat was different from that of an artificially labelled trilinoleate. The results shall be used for the adjustment and the correction of the base line in 13C-breath tests, especially with patients under parenteral nutrition.

Macrocycles are interesting molecules with unique features due to their conformationally constrained yet flexible ring structure. This characteristic poses a difficult challenge for computational modeling studies since they rely on accurate structural descriptions. In particular, molecular docking calculations suffer from the lack of ring flexibility during pose generation, which is often compensated by using pregenerated ligand conformer ensembles. Moreover, receptor structures are mainly treated rigidly, which limits the use of many docking tools. In this study, we optimized our previous molecular dynamics-based sampling and docking pipeline specifically designed for the accurate prediction of macrocyclic compounds. We developed a dihedral classification procedure for in-depth conformational analysis of the macrocyclic rings and extracted structural ensembles that were subsequently docked in both bound and unbound protein structures employing a fully flexible approach. Our results suggest that including a ring conformer close to the bound state in the starting ensemble increases the chance of successful docking. The bioactive conformations of a diverse set of ligands could be predicted with high and decent accuracy in bound and unbound protein structures, respectively, due to the incorporation of full molecular flexibility in our approach. The remaining unsuccessful docking calculations were mainly caused by large flexible substituents that bind to surface-exposed binding sites, rather than the macrocyclic ring per se and could be further improved by explicit molecular dynamics simulations of the docked complex.