MDockPeP: An ab‐initio protein–peptide docking server

Abstract

Protein-peptide interactions play a crucial role in a variety of cellular processes. The protein-peptide complex structure is a key to understand the mechanisms underlying protein-peptide interactions and is critical for peptide therapeutic development. We present a user-friendly protein-peptide docking server, MDockPeP. Starting from a peptide sequence and a protein receptor structure, the MDockPeP Server globally docks the all-atom, flexible peptide to the protein receptor. The produced modes are then evaluated with a statistical potential-based scoring function, ITScorePeP. This method was systematically validated using the peptiDB benchmarking database. At least one near-native peptide binding mode was ranked among top 10 (or top 500) in 59% (85%) of the bound cases, and in 40.6% (71.9%) of the challenging unbound cases. The server can be used for both protein-peptide complex structure prediction and initial-stage sampling of the protein-peptide binding modes for other docking or simulation methods. MDockPeP Server is freely available at http://zougrouptoolkit.missouri.edu/mdockpep.

A Multiple Peptides Vaccine against nCOVID-19 Designed from the Nucleocapsid phosphoprotein (N) and Spike Glycoprotein (S) via the Immunoinformatics Approach

“…The total population coverage percentage of the promising peptides was above 98%. The remaining MHC I and MHC II According to the MDockPeP [29] and HPEPDOCK [30] servers prediction, the spike peptide (FTISVTTEI) has the highest binding affinity to the MHC I HLA-B1503 allele and the spike peptide (MIAQYTSAL) has the highest binding affinity to the MHC I HLA-C1203 allele. The Nucleocapsid peptide (KTFPPTEPK) has the highest binding affinity to the MHC I HLA-A0202 allele ( Table 6).…”

“…To validate the results of molecular docking, MDockPeP [29] and HPEPDOCK [30][31][32][33][34] servers were used. The MDockPeP server predicts the MHC-Peptides interaction by "docking the peptides onto the whole surface of protein independently and flexibly using a novel the conformation restriction in its novel iterative approach.…”

“…The MDockPeP server predicts the MHC-Peptides interaction by "docking the peptides onto the whole surface of protein independently and flexibly using a novel the conformation restriction in its novel iterative approach. It ranks the docked Peptides via the ITScorePeP scoring function that uses the known protein-peptide complex structures in the calculations" [29]. In contrast, HPEPDOCK uses "a hierarchical flexible peptide docking approach" to predict the MHC-Peptides interaction [30].…”

“…The modeled MHC structures were prepared for the docking via Cresset Flare software [28] at the normal type calculation method. To dock the predicted peptides, the MDockPeP [29] and HPEPDOCK [30][31][32][33][34] servers were used. The predicted peptides were submitted as amino acid sequences.…”

Improved Modeling of Peptide-Protein Binding through Global Docking and Accelerated Molecular Dynamics Simulations

“…Molecular docking has proven useful in predictions of peptide-protein complex conformations (Ciemny et al, 2018). The commonly used approaches include template-based docking such as GalaxyPepDock (Lee et al, 2015), local docking of peptides to pre-defined binding sites such as Rosetta FlexPepDock (Raveh et al, 2011), HADDOCK (Trellet et al, 2013) and MDockPep (Xu et al, 2018), and global docking of free peptide binding to proteins such as CABS-dock (Kurcinski et al, 2015), PIPER-FlexPepDock and PeptiDock . The template-based docking is highly efficient, but often limited to the availability of templates (Lee et al, 2015).…”