ClusPro PeptiDock: efficient global docking of peptide recognition motifs using FFT

Abstract

SummaryWe present an approach for the efficient docking of peptide motifs to their free receptor structures. Using a motif based search, we can retrieve structural fragments from the Protein Data Bank (PDB) that are very similar to the peptide’s final, bound conformation. We use a Fast Fourier Transform (FFT) based docking method to quickly perform global rigid body docking of these fragments to the receptor. According to CAPRI peptide docking criteria, an acceptable conformation can often be found among the top-ranking predictions.Availability and ImplementationThe method is available as part of the protein-protein docking server ClusPro at https://peptidock.cluspro.org/nousername.php.Supplementary information Supplementary data are available at Bioinformatics online.

High-resolution global peptide-protein docking using fragments-based PIPER-FlexPepDock

“…Step A | Generation of fragment set to represent the peptide conformer ensemble: In a previous study we have shown that the bound peptide conformation can be well represented by extraction of short fragments from the PDB based on information of known binding sequence motifs 24 . Here we have generalized this approach beyond motifs, using fragment libraries selected by the Rosetta fragment picker protocol 22 based on sequence and secondary structure similarity (see Methods ).…”

“…Motivated by our recent advance in global peptide docking using a motif-focused approach 24 we ventured into the development of a more generalized protocol. We initially calibrated our docking approach on a small representative set of nine peptide– protein complexes (highlighted in bold in Table 1 ; see also Supplementary Table S1A ).…”

“…(Note that the gray circles are taken from the top-ranked models of the full PIPER run based on density clustering [see Methods and Porter et al . 24 ]), while the distributions represent the subset of models that served as starting structures for the models selected after FlexPepDock refinement).…”

“…The recently published IDP-LZerD protocol models the binding of long disordered segments to structured proteins using the Rosetta fragment picker protocol 22 to generate fragments of 9-residue overlapping windows followed by LZerD 23 rigid-body docking and molecular dynamics refinement 17 . Finally, we have recently advanced a novel, global motif-based peptide fragment docking approach, PeptiDock 24 , in which peptide binding motif information rather than secondary structure propensity is used to extract fragments from the Protein Data Bank (PDB 25 ), which are then docked to the receptor using PIPER rigid body docking 26 , followed by minimization using CHARMM 27 .…”

An Envelope Protein of a Prokaryotic Organelle Function towards Conserving Catalytic Activity of the Native Enzyme at Higher Temperatures

“…10 hydrogen bonds (Table S4) and 1 salt bridge hold the complex together. We use PIPER-Flex PEP dock (32)(33)(34) to see the interactions between first 15 amino acids of N-terminal region of PduB' with D subunit of the enzyme (Fig. 6).…”