Skip to content
DraconiticResearch
Search Sources API
201,683 studies31 sourcesUpdated 53 min ago
Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Targeting the ERK2 D-Recruitment Site with Anticancer Peptides from the DRAMP Database: An Integrated In Silico Study

  • Nahlah Makki Almansour1
  • Mahmoud A. A. Ibrahim2,3,4
4 affiliations
  1. 1Department of Biology, College of Science, University of Hafr Al Batin, Hafr Al Batin 1803, Saudi Arabia
  2. 2Computational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University, Minia 61519, Egypt
  3. 3School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa
  4. 4Department of Supportive Requirements, University of Technology and Applied Sciences, Nizwa 611, Oman
Open at sourceDOICite

Abstract

ERK2 is a central regulator of the MAPK pathway, governing cell proliferation, differentiation, and survival, and its aberrant activation is a recognized driver of cancer progression. ATP-competitive ERK2 inhibitors suffer from limited selectivity owing to the highly conserved kinase active site, whereas the ERK2 D-recruitment site (DRS), a non-catalytic docking surface mediating substrate recruitment, offers a more selective route to pathway modulation. Herein, the DRAMP database was screened, yielding 31 peptides with putative anticancer activity within the 5–15 residue range, which were docked towards the ERK2 DRS employing HADDOCK2.4. The protocol was first validated by reproducing the crystallographic binding mode of the co-crystallized KIM-MAP3 peptide. Peptides meeting the applied docking-score threshold were advanced to molecular dynamics simulations, followed by MM-GBSA binding energy calculations. Over 200 ns trajectories, DRAMP03987, DRAMP03983, and DRAMP03985 bound ERK2 more favorably than the reference KIM-MAP3 peptide, with ΔGbinding values of −71.2, −65.1, and −63.1 kcal/mol, respectively, versus −51.5 kcal/mol. Energetic and structural analyses indicated sustained occupancy of the DRS throughout the simulations, while in silico physicochemical profiling revealed preliminary physicochemical characteristics. Collectively, these findings highlight the potential of the identified peptides as ERK2 DRS-binding candidates, warranting further experimental investigation.

Related

  1. TTPdb: a comprehensive database of targeted therapeutic peptides
    Yang Zhang, Xuedong Li, Weimin Lu +16
    Nucleic Acids ResearchPeer-reviewedCC BY-NC 4.0Full textMolecular biology & gene regulationCrossref
  2. In Vitro Anticancer Activity and Integrated Multi-Target Computational Analysis of Ylang-Ylang Essential Oil Against Breast Cancer
    Mohamed Chebaibi, Amine Elbouzidi, Mohamed Taibi +10
    International journal of molecular sciencesPeer-reviewedCC BYFull textGeneral biochemistryEurope PMC
  3. Pep2Net: an integrated peptide knowledge base and cross-attention model for multi-task prediction of peptides
    Boyan Zheng, Jiahao Yuan, Yuzhou Wang +4
    Genome BiologyPeer-reviewedCC BY-NC-ND 4.0Molecular biology & gene regulationCrossref
  4. PP2A targeting: balancing anticancer potential and neurological risk.
    Margarita Chigriai, Nina Kraskovskaya, Anastasia Bolshakova +3
    Frontiers in cell and developmental biologyPeer-reviewedCC BYFull textMolecular biology & gene regulationEurope PMCPMC
  5. Inhibitory, Anticancer Efficacy and Structural Insights of a Novel Ethyl 1-Hydroxy-3-Oxo-1-Phenylisoindoline-2-Sulfonate Compound Selectively Targeting Human CA IX and CA XII Carbonic Anhydrase, Ferroptosis-Mediated Cell Death.
    Funda Keteci, Songul Bayrak, Ufuk Atmaca +3
    Cell biochemistry and functionPeer-reviewedCC BYFull textMolecular biology & gene regulationEurope PMCPMC

Cite

BibTeXRIS
BibTeX
@article{almansour2026targeting,
  title = {{Targeting the ERK2 D-Recruitment Site with Anticancer Peptides from the DRAMP Database: An Integrated In Silico Study}},
  author = {Nahlah Makki Almansour and Mahmoud A. A. Ibrahim},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27219532},
  url = {https://www.mdpi.com/1422-0067/27/21/9532},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Targeting the ERK2 D-Recruitment Site with Anticancer Peptides from the DRAMP Database: An Integrated In Silico Study
AU  - Nahlah Makki Almansour
AU  - Mahmoud A. A. Ibrahim
PY  - 2026
DA  - 2026/10/25
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27219532
UR  - https://www.mdpi.com/1422-0067/27/21/9532
AB  - ERK2 is a central regulator of the MAPK pathway, governing cell proliferation, differentiation, and survival, and its aberrant activation is a recognized driver of cancer progression. ATP-competitive ERK2 inhibitors suffer from limited selectivity owing to the highly conserved kinase active site, whereas the ERK2 D-recruitment site (DRS), a non-catalytic docking surface mediating substrate recruitment, offers a more selective route to pathway modulation. Herein, the DRAMP database was screened, yielding 31 peptides with putative anticancer activity within the 5–15 residue range, which were docked towards the ERK2 DRS employing HADDOCK2.4. The protocol was first validated by reproducing the crystallographic binding mode of the co-crystallized KIM-MAP3 peptide. Peptides meeting the applied docking-score threshold were advanced to molecular dynamics simulations, followed by MM-GBSA binding energy calculations. Over 200 ns trajectories, DRAMP03987, DRAMP03983, and DRAMP03985 bound ERK2 more favorably than the reference KIM-MAP3 peptide, with ΔGbinding values of −71.2, −65.1, and −63.1 kcal/mol, respectively, versus −51.5 kcal/mol. Energetic and structural analyses indicated sustained occupancy of the DRS throughout the simulations, while in silico physicochemical profiling revealed preliminary physicochemical characteristics. Collectively, these findings highlight the potential of the identified peptides as ERK2 DRS-binding candidates, warranting further experimental investigation.
SN  - 1422-0067
ER  -