title: Secondary structure assignment for conformationally irregular peptides: comparison between DSSP, STRIDE and KAKSI.
abstract: Secondary structure assignment codes were built to explore the regularities associated with the periodic motifs of proteins, such as those in backbone dihedral angles or in hydrogen bonds between backbone atoms. Precise structure assignment is challenging because real-life secondary structures are susceptible to bending, twist, fraying and other deformations that can distance them from their geometrical prototypes. Although results from codes such as DSSP and STRIDE converge in well-ordered structures, the agreement between the secondary structure assignments is known to deteriorate as the conformations become more distorted. Conformationally irregular peptides therefore offer a great opportunity to explore the differences between these codes. This is especially important for unfolded proteins and intrinsically disordered proteins, which are known to exhibit residual and/or transient secondary structure whose characterization is challenging. In this work, we have carried out Molecular Dynamics simulations of (relatively) disordered peptides, specifically gp41659-671 (ELLELDKWASLWN), the homopeptide polyasparagine (N18), and polyasparagine dimers. We have analyzed the resulting conformations with DSSP and STRIDE, based on hydrogen-bond patterns (and dihedral angles for STRIDE), and KAKSI, based on α-Carbon distances; and carefully characterized the differences in structural assignments. The full-sequence Segment Overlap (SOV) scores, that quantify the agreement between two secondary structure assignments, vary from 70% for gp41659-671 (STRIDE as reference) to 49% for N18 (DSSP as reference). Major differences are observed in turns, in the distinction between α and 310 helices, and in short parallel-sheet segments.
authors.affiliation: Department of Physics, North Carolina State University, Raleigh, NC 27695, United States; Center for High Performance Simulations (CHiPS), North Carolina State University, Raleigh, NC 27695, United States.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Physics, North Carolina State University, Raleigh, NC 27695, United States; Center for High Performance Simulations (CHiPS), North Carolina State University, Raleigh, NC 27695, United States. Electronic address: sagui@ncsu.edu.
authors.forename: Celeste
authors.initials: C
authors.lastname: Sagui
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D003198:Computer Simulation; D006860:Hydrogen Bonding; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012984:Software
chemical_list: D000596:Amino Acids; D010455:Peptides
keywords: Asparagine; Intrinsically disordered proteins; Residual transient secondary structure; gp41