Interaction of small molecules with proteins in silico

Computational methods are increasingly used in biomedical research, including toxi- cological research. They are used to search for new molecules for a particular phar- macological target or to optimize the properties of known active molecules. The main methods used in these areas are molecular docking and molecular dynamics. New reactivators of butyrylcholinesterase inhibited by nerve agents were sought by methods of virtual screening. This reactivators would be applicable in prophylaxis and therapy of nerve agents poisonings. By combining the techniques of semi-flexible and flexible docking, two new structures were proposed that should specifically re- activate the inhibited butyrylcholinesterase. In addition, a virtual screening of cyclophilin D inhibitors was performed. These compounds could be used as drugs for Alzheimer's disease. Based on the availability of a huge number of crystallographic data, we decided to use a pharmacophore for the primary screening of a large database of small molecules. Molecular docking was employed in the second search phase. At the same time, we focused on the physicochemical properties of molecules. Four ligands have been found that should be inhibitors of cyclophilin D bioavailable in the central nervous system. Flexible molecular docking was used to optimize the..