Particularly to understand the interaction between both receptors as well as ligands, a pharmacophore is essential. Firstly, It is an important feature in the design of new drugs for the treatment of a specific disease. Moreover, Pharmacophore is defined as the essential geometric arrangement of atoms or functional groups necessary to produce a given biological response. Further, The strict IUPAC definition of a pharmacophore is: A pharmacophore is the ensemble of steric as well as electronic features that is necessary to ensure the optimal supramolecular interactions with a specific biological target structure and to trigger (or to block) its biological response.
According to the definition, the interactions of bioactive molecules with their targets are represented via a three-dimensional (3D) arrangement and this arrangement has some feature that defines interaction type. These interaction types include the formation of hydrogen bonds, charged interactions, metal interactions, or hydrophobic and aromatic contacts.
How can pharmacophores help in designing of drug?
Further Pharmacophore provides information in drug design and as a 3D query in searching databases containing drug-like small organic molecules to identify active and specific inhibitors. Moreover, Drug design is a step-by-step process very important in biopharmaceutical field. Therefore scientists using computer based pharmacophore modelling to select the bioactive substance.
Next Drug design is of two types; Firstly structure-based drug design and Secondly ligand based drug design, ligand based drug design relies on the knowledge of known bioactive molecule that bind to the biological target. Ligand based drug design uses pharmacophore features (hydrogen bonds, charged interactions, metal interactions, or hydrophobic and aromatic contacts) to design drugs. Pharmacophore modelling is done by online available bioinformatics tools, local research and platform.
This new computational strategy is characterized by a multi-step design process: 1) screening of a specific biological target for a crystal structure in database, 2) pharmacophore modeling and virtual computational screening, by using public domain databases of bioactive compounds in order to find a promising molecule that could become a new potential medicine. 3) molecular and biological evaluation, to check the compounds selected by virtual screening, for their biological properties to trace their origin and underline their most important physical-chemical features, an enzyme-catalyzed metabolic pathway predictor server to highlight and identify their biosynthetic-metabolic pathways and investigating the biotransformation of best candidates, analyzing their metabolites and their potential biological activity.
Then, ADMET/toxicity predictor server is applying the Lipinski-five rule filters is used to calculate the bioavailability the ADMET/toxicity properties. After this evaluation, a molecule with good bioavailability, good predicted bioactivity and good ADMET properties are considered as hit compound or drug. Pharmacophore approach accelerated drug designing process. Nowadays, personalised medicines have been developing according to patients’ genetic profile on the basis of the pharmacophore approach. Rasa life science informatics is one-stop solution for computer aided drug designing training course and computational drug discovery services.
References:
1.Khedkar, Santosh A., Alpeshkumar K. Malde, Evans C. Coutinho, and Sudha Srivastava. “Pharmacophore modeling in drug discovery and development: an overview.” Medicinal Chemistry 3, no. 2 (2007): 187-197.
2.Acharya, Chayan, Andrew Coop, James E Polli, and Alexander D MacKerell. “Recent advances in ligand-based drug design: relevance and utility of the conformationally sampled pharmacophore approach.” Current computer-aided drug design 7, no. 1 (2011): 10-22.
