Abstract
Five peptides previously suggested to possess polyproline II (PPII) structure have here been investigated by using atomistic molecular dynamics simulations to compare how well four different force fields known for simulating intrinsically disordered proteins relatively well (Amber ff99SB-disp, Amber ff99SB-ILDN, CHARM36IDPSFF, and CHARMM36m) can capture this secondary structure element. The results revealed that all force fields sample PPII structures but to different extents and with different propensities toward other secondary structure elements, in particular, the β-sheet and “random coils”. A cluster analysis of the simulations of histatin 5 also revealed that the conformational ensembles of the force fields are quite different. We compared the simulations to circular dichroism and nuclear magnetic resonance spectroscopy experiments and conclude that further experiments and methods for interpreting them are needed to assess the accuracy of force fields in determining PPII structure.
Highlights
Disordered proteins and regions (IDPs and IDRs) recognized as natively unfolded proteins and peptides are characterized by the lack of a well-defined tertiary structure in aqueous solution
Despite IDPs often being thought of as “unordered”, studies originating from the 1970s discovered that a few natively unfolded peptides possessed some degree of local order in their backbones, identified as the left-handed polyproline II (PPII) helix.[5]
One of the more recognized occurrences of the PPII helix might be as being part of the triple-helix structure of collagen, where it helps stabilize the collagen structure,[7] and specific efforts have been devoted to optimizing computational models for collagen.[8,9]
Summary
Disordered proteins and regions (IDPs and IDRs) recognized as natively unfolded proteins and peptides are characterized by the lack of a well-defined tertiary structure in aqueous solution. Their structural properties are known to vary significantly, which makes it difficult to study them by standard methods. One of the more recognized occurrences of the PPII helix might be as being part of the triple-helix structure of collagen, where it helps stabilize the collagen structure,[7] and specific efforts have been devoted to optimizing computational models for collagen.[8,9] Another well-known and important property of the PPII helix has been observed in the binding to SH3 domains,[10] where it facilitates and mediates protein−protein interactions.[11,12]
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