**1. Introduction**

Proteins are large biomolecules and macromolecules nexus, comprising long chains of different amino acids, thereby conferring proteins specific roles to perform forming essential component of working machinery. Proteins perform vital functions including, catalyzing metabolic reactions, DNA replication, normal structure of the cellular components, response to stimuli, catalyzes, enzymes, performing metabolic activities, and as transport molecules [1]. Although proteins are similar in function yet differ in configuration owing to particular encoding gene of nucleotide sequence and further ensembles protein folding and achieving its characteristic 3D structure or typical native conformation of protein. Protein primarily exist in four forms: primary, secondary, tertiary, and quaternary,

whereas some researchers have reported the fifth form of protein structure called quinary structure [2]. The primary structure comprises of linear chain of amino acids. Secondary structure contains amino acid chains stabilized by hydrogen bonds, forming the polypeptide backbone creating alpha-helix and beta-pleated sheets of the secondary structure. Tertiary structure is determined by the interactions of side chains from the polypeptide backbone [3]. The quaternary structure is formed *via* side-chain interactions between two or more polypeptides [4]. Quinary structure has been identified and refers to the features of protein surfaces that are shaped by evolutionary adaptation [2].

Proteins are dynamic objects, and they arrange themselves in certain conformations to perform correct functions. With respect to structural rearrangements, the structures are referred to as conformation and transitions in between are called conformational changes [5]. Protein folding is ineluctable phenomenon to generate biologically active protein achieving its characteristic structure. Molecular interactions, such as hydrophobic effects, Vander Waals forces, H-bonds, and hydrostatic interactions, exist stably maintaining folded proteins in position and structure. These interactions may either be favorable or unfavorable [6]. The favorable interactions include primarily the enthalpy from Vander Waals packing interactions; secondly, hydrophobic effect or entropy; thirdly, gain of protein-protein Hydrogen bonds; and lastly, electrostatic effects. Unfavorable interaction series include protein conformational entropy and loss of protein-water H-bonding [4, 7]. The correct folding of protein is necessary to perform particular function. Ribosomes and endoplasmic reticulum plays role in synthesizing of proteins and ensures proper folding of the proteins and degrades unfolded protein by various mechanisms (**Figure 1**) [8–10].

#### **Figure 1.**

*Depicting the normal binding of the protein when correctly folded and protein structure when misfolding of protein occurs.*
