against the enzyme, pharmacophore approach or the docking with the random inhibitor molecules from the different chemical libraries. Top selected inhibitor molecules can further validated in the in-silico toxicity analysis and pharmacokinetic parameters. The best molecule can be tested further in the wet lab experiment to validate the computational results and a series of clinical trials are needed before allowing therapeutic applications.

Each step of the computer aided drug design can be performed by multiple softwares with different algorithms. To understand the whole process of computer aided drug design, we will take an example of an enzyme and try to design the inhibitors. This complete process has following steps:

1. Strutural Determination of the target enzyme

A. Experimental Methods: X-ray crystallography and NMR spectroscopy are the two methods can be used to determine the 3-dimensional structure of the target enzyme.

I suggests to go through the following articles to get full detail of these structure solution processes. 1. RRM-RNA recognition: NMR or crystallography …and new findings. Daubner GM, Cléry A, Allain FH. Curr Opin Struct Biol. 2013 Feb;23(1):100-8. PMID: 23253355. 2. Protein structure determination by magic-angle spinning solid-state NMR , and insights into the formation, structure, and stability of amyloid fibrils. Comellas G, Rienstra CM. Annu Rev Biophys. 2013;42:515-36. PMID: 235277.

B. Homology modeling- This is a useful and fast structural solution method where the sequence similarities between the template and the target enzyme is used to model the 3-dimensional structure of the target enzyme. The homology modeling exploits the idea that the amino acid sequence of a protein directs the folding of the molecule to adopt a suitable 3-dimensional conformation with minimum free energy.

Different steps in homology modeling- Several softwares are available to perform homology modeling of a given protein sequence (Table 40.1). Homology modeling is a multistep process and it has following steps:

Step I : Identification of a suitable target- Identification of a suitable template structure is the most crucial step to generate a good quality homology model. The target sequence is blasted into the protein strucuture database (www.rcsb.org) using PSI-Blast.