Integrated In Silico Analysis Reveals ABC Transporter ATP-Binding Protein as a Therapeutic Target in Helicobacter pylori
- 1Nitte (Deemed to be University) , , Deralakatte , , ,
- 2Kuvempu University , , Shankaraghatta , , ,
- 3Nitte (Deemed to be University) , , Deralakatte , ,
Abstract
Helicobacter pylori remains a major cause of gastric diseases, while increasing antimicrobial resistance highlights the need for novel therapeutic targets. Here, we developed a comprehensive computational target-prioritization framework integrating Rosetta Stone domain-fusion analysis, subtractive genomics, metabolic pathway mapping, structural modeling, and molecular dynamics simulations to identify pathogen-specific drug targets in H. pylori J99. Twelve conserved domain families comprising 746 proteins were identified, and domain abundance showed a weak negative correlation with versatility (r = −0.327), suggesting functional specialization through domain expansion. Sequential filtering based on essentiality, nonhomology to the human proteome and gut microbiota, subcellular localization, and druggability prioritized five candidate proteins, with the ATP-binding protein AAD06727.1 emerging as the most promising target. AlphaFold2 modeling produced a high-confidence structure containing a conserved nucleotide-binding pocket. Molecular docking identified 5′-fluorosulfonylbenzoyl-5′-adenosine (FSBA) as the highest-affinity ligand (−7.3 kcal mol–1), outperforming ATP and verapamil. Triplicate 1 μs molecular dynamics simulations of apo and halo AAD06727.1 demonstrated stable rmsd, RMSF, radius of gyration, solvent-accessible surface area, hydrogen-bond occupancy, and principal component profiles, indicating preservation of structural integrity following ATP binding. Comparative simulations with the human ABCA12 nucleotide-binding domain showed conserved global architecture while revealing distinct ligand-recognition characteristics. Together, these findings identify AAD06727.1 as a structurally stable, pathogen-specific ATP-binding protein that represents a promising candidate for future structure-guided anti-H. pylori drug development.
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BibTeX
@article{kumar2026integrated,
title = {{Integrated In Silico Analysis Reveals ABC Transporter ATP-Binding Protein as a Therapeutic Target in Helicobacter pylori}},
author = {Manish Kumar and H. S. Santosh Kumar and Ballamoole Krishna Kumar and Veena A. Shetty and Pavan Gollapalli},
journal = {ACS omega},
year = {2026},
month = sep,
doi = {10.1021/acsomega.6c05087},
url = {https://europepmc.org/article/PMC/PMC13670296},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Integrated In Silico Analysis Reveals ABC Transporter ATP-Binding Protein as a Therapeutic Target in Helicobacter pylori
AU - Manish Kumar
AU - H. S. Santosh Kumar
AU - Ballamoole Krishna Kumar
AU - Veena A. Shetty
AU - Pavan Gollapalli
PY - 2026
DA - 2026/09/29
JO - ACS omega
DO - 10.1021/acsomega.6c05087
UR - https://europepmc.org/article/PMC/PMC13670296
AB - Helicobacter pylori remains a major cause of gastric diseases, while increasing antimicrobial resistance highlights the need for novel therapeutic targets. Here, we developed a comprehensive computational target-prioritization framework integrating Rosetta Stone domain-fusion analysis, subtractive genomics, metabolic pathway mapping, structural modeling, and molecular dynamics simulations to identify pathogen-specific drug targets in H. pylori J99. Twelve conserved domain families comprising 746 proteins were identified, and domain abundance showed a weak negative correlation with versatility (r = −0.327), suggesting functional specialization through domain expansion. Sequential filtering based on essentiality, nonhomology to the human proteome and gut microbiota, subcellular localization, and druggability prioritized five candidate proteins, with the ATP-binding protein AAD06727.1 emerging as the most promising target. AlphaFold2 modeling produced a high-confidence structure containing a conserved nucleotide-binding pocket. Molecular docking identified 5′-fluorosulfonylbenzoyl-5′-adenosine (FSBA) as the highest-affinity ligand (−7.3 kcal mol–1), outperforming ATP and verapamil. Triplicate 1 μs molecular dynamics simulations of apo and halo AAD06727.1 demonstrated stable rmsd, RMSF, radius of gyration, solvent-accessible surface area, hydrogen-bond occupancy, and principal component profiles, indicating preservation of structural integrity following ATP binding. Comparative simulations with the human ABCA12 nucleotide-binding domain showed conserved global architecture while revealing distinct ligand-recognition characteristics. Together, these findings identify AAD06727.1 as a structurally stable, pathogen-specific ATP-binding protein that represents a promising candidate for future structure-guided anti-H. pylori drug development.
SN - 2470-1343
ER -