Structure Based Design
In addition to standard protocol of Computer Aided Drug Design (CADD) aimed at small molecules, concept of structure based design has been applied also in peptidomimetic and on proteins.
For small molecules both, modifications of lead or predefined compounds as well as finding most potent molecule from library of compounds by virtual screening have been comprehended. In order to enhance the chance of finding most proper variations of altered compounds, alongside with manual modification based on the knowledge of structure-function relationship, library of chemical fragment and combinatorial gene-like technique based on SMILES notation of chemicals are being successfully used.
Structural information is also an excellent base for targeted alterations of protein. They consist not only in chemical modifications as in the case of small molecules but also in a mutation of selected amino-acids[ ]. Another very promising possibility is to combine both approaches in a way that amino-acids are first mutated and only then is the protein subjected to chemical modification. Finely tuned selection of residues for mutations based on the knowledge of protein function and structure together with proper choice of chemical substitution group enables to selectively steer protein properties.