The serpins (serine proteinase inhibitors) are structurally similar but functionally diverse proteins that fold into a conserved structure and employ a unique suicide substrate-like inhibitory mechanism. Serpins play absolutely critical role in the control of proteases involved in the inflammatory, complement, coagulation and fibrinolytic pathways and are associated with many conformational diseases. Serpin's native state is a metastable state which transforms to a more stable state during its inhibitory mechanism. Serpin in the native form is in the stressed (S) conformation that undergoes a transition to a relaxed (R) conformation for the protease inhibition. During this transition the region called as reactive center loop which interacts with target proteases, inserts itself into the center of β-sheet A to form an extra strand. Serpin is delicately balanced to perform its function with many critical residues involved in maintaining metastability. However due to its typical mechanism of inhibition, naturally occurring serpin variants produces conformational instability that allows insertion of RCL of one molecule into the β-sheet A of another to form a loop-sheet linkage leading to its polymerization and aggregation. Thus understanding the molecular basis and amino acid involved in serpin polymerization mechanism is critical to devising strategies for its cure.

All physiological events in living organisms originated as specific chemical/biochemical signals on the cell surface and transmitted into the cytoplasm. This signal is translated within milliseconds–hours to a specific and unique order required to maintain optimum performance and homeostasis of living organisms. Examples of daily biological functions include neuronal communication and neurotransmission in the process of learning and memory, secretion (hormones, sweat, and saliva), muscle contraction, cellular growth, differentiation and migration during wound healing, and immunity to fight infections. Among the different transducers for such life-dependent signals is the large family of G protein-coupled receptors (GPCRs). GPCRs constitute roughly 800 genes, corresponding to 2% of the human genome. While GPCRs control a plethora of pathophysiological disorders, only approximately one-third of GPCR families have been deorphanized and characterized. Recent drug data show that around 40% of the recommended drugs available in the market target mainly GPCRs. In this review, we presented how such system signals, either through G protein or via other players, independent of G protein, function within the biological system. We also discussed drugs in the market or clinical trials targeting mainly GPCRs in various diseases, including cancer.

Docking of various therapeutically important chemical entities to the specific target sites offers a meaningful strategy that may have tremendous scope in a drug design process. For a thorough understanding of the structural features that determine the strength of bonding between a ligand with its receptor, an insight to visualize binding geometries and interaction is mandatory. Bioinformatical as well as graphical software 'PyMOL' in combination with the molecular docking suites Autodock and Vina allows the study of molecular combination to visualize and understand the structurebased drug design efforts. In the present study, we outlined a user friendly method to perform molecular docking using vina and finally the results were analyzed in pymol in both two as well as three-dimensional orientation. The operation bypasses the steps that are involved in docking using cygwin terminal like formation of gpf and dpf files. The simple and straight-forward operation method does not require formal bioinformatics training to apprehend molecular docking studies using AutoDock 4.2 program.

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Name of ligand Mol wt (g/mol)Structure and IUPAC names of compound R0 (Remdesivir) 602.583R1 618.582 2-ethylbutyl (2R)-2-[[[(2S,3R,4S,5S)-5-(4aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4dihydroxyoxolan-2-yl]methoxy-(4-hydroxyphenoxy)phosphoryl]amino]propanoate