Quick Guideline for Computational Drug Design

Bioinformatics is an emerging modern biology to solve the biological problems with the help of computational approaches by utilizing mathematical and statistical techniques. There are many databases of protein and gene sequences. The protein sequence can be retrieved from UniProt and 3D structure prediction can be performed by utilizing homology modeling, threading and ab initio. The predicted structures can be evaluated by utilizing numerous model evaluation tools.

The analyses of primary sequence (amino acid sequence) of protein always show logical insights for further studies. We can analyze a wide range of basic information including a prediction of repetitive sequences, the motif, domain, or active sites, and the ability to form a coiled-coiled structure by performing primary sequence analyses. Protparam, the primary sequence analysis tool was utilized to analyze the physicochemical properties of the selected protein.

The analyses of a secondary structure of protein always show logical insights for further studies. α-helices and β-sheets are considered as the major elements of secondary structure which are based on hydrogen bond donor and acceptor residues interactions. The secondary elements may provide information regarding the behavior of the proteins. ProFunc tool utilized to analyze the secondary structure of RASSf2.

The proteins having similar sequences may have similar structure” is the philosophy of sequences prediction techniques. The 3D structures have structural and functional importance for drug designing. Homology modeling, threading and ab initio approaches are the computational techniques to predict the 3D structure of the proteins for further studies. In this chapter, we will precisely elaborate numerous tools of 3D structure prediction.

The computational prediction of the protein 3D structures involves the mathematical modeling techniques based on statistical terms. That is why the resultant structures may have some structural issues related to β-sheets, α-helices, non-structural loops, amino acid chain angles and backbone psi, phi bond angles that pose potential energy constraints in the structure. The validation of the computationally predicted structure is mandatory that compares different parameters of the protein 3D structure with that of experimentally available protein structures. Here, in this chapter we will discuss the evaluation procedure of the 3D structures for their accuracy and physiochemistry by numerous available tools.

The structures of proteins generated experimentally or computationally are in a .pdb files and to visualize these structures are the key need of new era. The visualization of the predicted models helps to visualize including loops, α helices, β pleated sheets and turns for the better understanding of the structure. Numerous tools are available for visualizing the structures and also to edit or performing different functions as per the need of experiment. Here, we will focus on the basic visualizing functions by utilizing Chimera.

The molecular docking is a significant approach to computer-aided drug design coupled with structural biology. The ligand-protein docking analyses perform to predict the binding domains of a ligand with a protein.