Abstract
Protein structures are often represented as seen in crystals as (i) rigid macromolecules (ii) with helices, sheets and coils. However, both definitions are partial because (i) proteins are highly dynamic macromolecules and (ii) the description of protein structures could be more precise. With regard to these two points, we analyzed and quantified the stability of helices by considering α-helices as well as 310-and π-helices. Molecular dynamic (MD) simulations were performed on a large set of 169 representative protein domains. The local protein conformations were followed during each simulation and analyzed. The classical flexibility index (B-factor) was confronted with the MD root mean square flexibility (RMSF) index. Helical regions were classified according to their level of helicity from high to none. For the first time, a precise quantification showed the percentage of rigid and flexible helices that underlie unexpected behaviors. Only 76.4% of the residues associated with α-helices retain the conformation, while this tendency drops to 40.5% for 310-helices and is never observed for π-helices. α-helix residues that do not remain as an α-helix have a higher tendency to assume β-turn conformations than 310-or π-helices. The 310-helices that switch to the α-helix conformation have a higher B-factor and RMSF values than the average 310-helix but are associated with a lower accessibility. Rare π-helices assume a β-turn, bend and coil conformations, but not α-or 310-helices. The view on π-helices drastically changes with the new DSSP (Dictionary of Secondary Structure of Proteins) assignment approach, leading to behavior similar to 310-helices, thus underlining the importance of secondary structure assignment methods.
Highlights
Before the first protein 3D structure was solved at atomic resolution [1], Pauling and Corey provided evidence that polypeptide chains can adopt a limited number of repetitive local protein structures stabilized by intramolecular hydrogen bonds (HB) [2,3,4]
A databank of 169 X-ray structures taken from Protein DataBank (PDB) [44] was extracted using ASTRAL 2.03 [45,46] (PDB ids and corresponding chain are provided in the Supplementary data S1)
Protein Blocks (PBs) assignment was carried out for every residue obtained from every snapshot extracted from Molecular dynamic (MD) simulations using our PBxplore tool at GitHub [61]. From this description we developed a useful measure that helps in quantifying the flexibility of each amino acid, the so-called Neq [57]
Summary
Before the first protein 3D structure was solved at atomic resolution [1], Pauling and Corey provided evidence that polypeptide chains can adopt a limited number of repetitive local protein structures stabilized by intramolecular hydrogen bonds (HB) [2,3,4]. The two major local folds are: (i) the α-helix (or 3.613 helix) with HB between amino acid residues i and i +4, and (ii) the β-sheet composed of extended strands with. They roughly represent 1/3rd and 1/5th of the residues found in proteins, respectively. Since their discovery, extensive explorations have been conducted to better understand their formation and their role in the kinetics of protein folding.
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