Quick Guideline for Computational Drug Design (Revised Edition)

Bioinformatics is an emerging field of modern biology that solves biological problems with the help of computational approaches by utilizing mathematical and statistical techniques. There are many available 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.

Protein primary sequence analyses (amino acid sequence) always show logical insights for further studies. We can analyze a wide range of basic informative aspects, 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 Expasy, the primary sequence analysis tool, was utilized to analyze the physicochemical properties of PSEN2 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 was utilized to analyze the secondary structure of PSEN2.

“The proteins having similar sequences may have a 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 on numerous tools of 3D structure prediction.

The computational prediction of the protein 3D structures involves mathematical modeling techniques based on statistical terms that are 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, which 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 physio-chemistry by numerous available tools.

In recent years, in silico molecular-based docking techniques can improve the efficiency and different domains of research cost and other hits. Molecular docking has a key role in computer-aided drug design (CADD). Various key principles, tools, procedure, and application of molecular docking has been reported. Numerous paid and free tools are available for molecular docking analyses with a high level of biological data into scoring energy functions. MOE (molecular operating environment) is a drugbased visualization, simulation, docking, QSAR, and modeling software. MOE scientific domains are pharmacy, computational chemistry, biotechnology, and computational biology.

Protein-ligand interactional analyses are the molecular insights to understand biology at a molecular level. Proteins, as biological macromolecules, recognize their functions by interacting with themselves or other small molecules to build a specific complex with high affinity and specificity that forms a basic process in all living organisms. Therefore, the protein-ligand interactions need to be studied and analyzed that will be performed in this study through visualization tool (MOE).