In silico Studies of Biologically Active Molecules

Contemporary in silico (computer-aided) approaches to rational drug design and human health and environmental chemical risk assessment combine various ligand- and structure-based methods, including classical and three-dimensional (3D) quantitative structure–activity relationship (QSAR) models, pharmacophore and homology modelling, docking and virtual screening. These approaches are highly interdisciplinary and integrate knowledge from various disciplines in natural sciences. Their ultimate purpose is to quantitatively characterise the relationship between the compounds’ chemical structures and their effects, expressed by theoretical models, while the effect can be different—therapeutic, toxic, etc. In silico approaches effectively help in understanding and elucidation of the mechanisms by which chemical compounds interact with target biomacromolecules, thereby explaining fundamental processes in the living organisms. The chapter describes main methods in the computer-aided design and computational toxicology. The methods are classified according to the information available for modelling. Several case studies are described to illustrate the application of various in silico methods alone or in a combination. The case studies summarize the most recent results of the authors related to development of in silico models, algorithms and software applications to important biologically active molecules, both small drugs and drug-like compounds, and biomacromolecules, including nuclear receptors.