title: A molecular dynamics strategy for CSαβ peptides disulfide-assisted model refinement.
abstract: Many cysteine-stabilized antimicrobial peptides from a variety of living organisms could be good candidates for the development of anti-infective agents. In the absence of experimentally obtained structural data, peptide modeling is an essential tool for understanding structure-activity relationships and for optimizing the bioactive moieties. Focusing on cysteine-rich peptide structures, we reproduced the case of structure predictions in the so-called midnight zone. We developed our protocol on a training set derived by clustering the available cysteine-stabilized αβ (CSαβ) structures in nine different representative families and tested it on peptides randomly selected from each family. Starting from draft models, we tested a structure-based disulfide predictor and we used cysteine distances as constraints during molecular dynamics. Finally, we proposed an analysis for final structure selection. Accordingly, we obtained a mean root mean square deviation improvement of 21% for the test set. Our findings demonstrate that it is possible to predict the network of disulfide bridges in cysteine-stabilized peptides and to use this result to improve the accuracy of structural predictions. Finally, we applied the methods to predict the structure of royalisin, a cysteine-rich peptide with unknown structure.
authors: a Department of Biology , University of Padova , Via Ugo Bassi 58/B, Padova 35131 , Italy.
authors: Marco
authors: http://orcid.org/0000-0001-8701-5632
authors: M
authors: Franzoi
authors: b Molecular Modeling Section (MMS), Department of Pharmaceutical and Pharmacological Sciences , University of Padova , Via Marzolo 5, Padova 35131 , Italy.
authors: Mattia
authors: http://orcid.org/0000-0003-3944-0313
authors: M
authors: Sturlese
authors: c Department of Chemical Sciences , University of Padova , Via Marzolo 1, Padova 35131 , Italy.
authors: Massimo
authors: M
authors: Bellanda
authors: c Department of Chemical Sciences , University of Padova , Via Marzolo 1, Padova 35131 , Italy.
authors: Stefano
authors: S
authors: Mammi
mesh_terms: D000818:Animals; D001516:Bees / Q000378:metabolism; D047169:Cyclotides / Q000737:chemistry*; D003545:Cysteine / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry*; D036341:Intercellular Signaling Peptides and Proteins; D056004:Molecular Dynamics Simulation; D011506:Proteins / Q000737:chemistry*; D013329:Structure-Activity Relationship; D032413:Viola / Q000378:metabolism
chemical_list: D047169:Cyclotides; D004220:Disulfides; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; C064722:royalisin; D003545:Cysteine
keywords: CSαβ; antimicrobial peptides; disulfides; molecular dynamics; structural prediction