Is the Folding Topology of a Protein Related to its Amino Acid Occurrence?

Proteins are molecular machines built from a polypeptide chain with capability to self-assemble into a compact 3D structure. This amazing capability is only exhibited by a subset of all the possible polypeptide chains built using the 20 natural amino acids so that, proteins in the living organisms are the result of years of natural selection (1). The physical basis of protein self-assembling or folding as is commonly referred, has puzzled researchers for the last fifty years and it is still a matter of debate (2, 3). Protein folding has been analyzed using methodologies that range from biophysical methods including structural, spectroscopic or computational to biochemical, including those of molecular biology. Present knowledge is the result of important research efforts basically focused on either understanding the structural features of known folded proteins, on the dynamics of the folding process or on the design of algorithms to predict the 3D structure of a protein from its sequence. These three aspects are closely related and need to be considered simultaneously, since prediction of the 3D structure of a protein involves a deep understanding of the structural features of folded proteins together with a solid knowledge of the driving forces involved in the folding process, including the role played by the solvent (4).

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