in Silico Approaches—Main Principles
At the heart of all in silicoapproaches is the understanding for existence of an objective relationship between the structure of the compound and its biological activity (BA). The quantification of this dependence for a particular series of compounds reflects the changes (Δ) in the structures S of the compounds that result in changes in their BA va
Classification of The in Silico Approaches
The classification depends on the level of information and knowledge available about the studied molecules. Table 1 summarises the classification of modern in silicoapproaches. In the table the term “ligand” is used to denote a molecule (mostly small one) that interacts with a biomacromolecule (receptor). In general, the following three modelling s
Classical QSAR Analysis: Hansch Analysis
Classical QSAR models are one of the mostly used in silico models in the rational drug design and computational toxicology. The models rely on the following basic assumptions: (a) all ligands belong to a homologous series of compounds; (b) all compounds act by the same mechanism on the receptor; (c) all compounds bind to the receptor active site in
3D QSAR Analysis: CoMFA and CoMSIA Approaches
The 3D QSAR aims at establishing a correlation between the biological activity and 3D properties (molecular fields) of a series of structurally related molecules. The concept of this analysis was first proposed by Cramer et al. as “a multidimensional statistical procedure for comparing the experimental property of a molecule with one or more of its
Pharmacophore Modelling
According to “Glossary of terms used in computational drug design” [32] a pharmacophore is an ensemble of steric and electronic features (pharmacophoric features) that is necessary to ensure the optimal supramolecular (noncovalent) interactions with a specific biological target and to trigger (or block) its biological response. Compared to the rest
Docking and Virtual Screening
These methods belong to the structure-based ones (Table 1) presuming a known 3D structure of the receptor of interest or of its complex with a ligand. Docking is a computational procedure aiming to find favourable binding configurations between a small to medium-sized ligand and the receptor of interest (usually a protein). A ligand configuration i