Research Updates on Protein Folding

The principle guiding protein to fold into its native conformation has been searched by biochemists, structural biologists, molecular biologists, and recently by bioinformaticians. They have discovered various facts and indicated to find the solution by coming decades. There are various challenges toward them, most importantly the existence of folding intermediates for only < 1 s due to which their isolation is an unapproachable task to carry out thorough analysis. However, kinetic characterization of folding intermediate has been successfully done using hydrogen exchange (HX) methods in number of cases. Various theoretical models have been given to elucidate protein folding pathways and their principles. Theoretical biologists are trying hard for the prediction of three-dimensional structure of native proteins from their amino-acid sequence by using principle of folding pathways. It is well understood that amino-acid sequence of the protein has got the code of three-dimensional structure of the native protein. The environmental factors comprising both physical (temperature, pressure) and chemical factors (salt, suitable solvent, pH, etc.) as well as presence of chaperones are the major factors which actually govern the correct protein folding. The alteration in any of these environmental characteristics can disrupt the structure via interference of the mechanism of folding. Protein folding is the cooperative action of foldons (small unfolding/refolding units) which defines the unit steps in folding pathway. There is stepwise addition of each foldon unit during folding in a sequential manner with each step being guided by attainment of stability. Finally, native protein with maximum stability and activity is generated.