Structure-based Drug Design
Abstract
In silico structure-based drug design techniques are fast and efficient methods to identify potential lead molecules (“hit” compounds) for biomolecular entities. If the protein active site is known, these techniques are used to identify molecules that bind to specific proteins (druglike compounds) or optimize compounds (leadlike compounds) to increase their selectivity and thermodynamic properties involved in the protein-ligand binding.
If the protein “natural” ligand is unknown, High Throughput Screening (HTS) techniques can be used to identify a set of compounds from a large database with potential drug properties against protein targets. If the ligands are known and in order to increase normally their inhibitory activity or change their scaffold, the computational hit/lead optimization and scaffold hopping procedures can help to obtain new suitable ligands binding to the query protein. At CCB, We have developed the hit/lead optimization method involving the addition, removal or replacement of chemical groups in the hit molecule.
Image displayed above is an illustration of the structural based drug-discovery algorithm developed at the CCB.
Summary of CCB's Involvement
Development of hit/lead optimization software
In collaboration with Mitsubishi-Tanabe Pharma. Corp., we have developed software for hit/lead optimization. For compound/protein complex structures, the compound reaction points are automatically detected in five simple reaction rules and attached the suitable building blocks which lead to increasing the inhibitory activity.
Development of fast screening program
In collaboration with Mitsubishi-Tanabe Pharma., we are developing a fast screening algorithm for structure based drug design (SBDD). This method will accelerate the detection of novel compounds and will help to reduce the drug discovery process. We are aiming to screen against a target protein many millions compounds from a large database in a relatively short period of time (one- two months).
