2026-10-13T22:12:34Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34028580 2026-09-30T02:04:45Z category_1 category_4 category_7 category_13 category_19 category_873 category_734 category_931 category_64 category_135 portal_63 item_type_6 month_year_09_2026

Integrated In Silico Analysis Reveals ABC Transporter ATP-Binding Protein as a Therapeutic Target in Helicobacter pylori Manish Kumar (50435) H. S. Santosh Kumar (25139793) Ballamoole Krishna Kumar (11307304) Veena A. Shetty (25139796) Pavan Gollapalli (9599543) Biophysics Biochemistry Medicine Genetics Pharmacology Chemical Sciences not elsewhere classified Biological Sciences not elsewhere classified Information Systems not elsewhere classified Cancer Computational Biology weak negative correlation sequential filtering based revealing distinct ligand principal component profiles metabolic pathway mapping accessible surface area 5 ′- adenosine 3 kcal mol specific drug targets pylori drug development novel therapeutic targets molecular dynamics simulations domain abundance showed confidence structure containing alphafold2 modeling produced comprehensive computational target findings identify aad06727 human abca12 nucleotide binding protein aad06727 therapeutic target halo aad06727 binding protein structural modeling pylori j99 human proteome future structure domain expansion conserved nucleotide comparative simulations promising target binding pocket − 0 versatility (< subtractive genomics subcellular localization structurally stable specific atp recognition characteristics r </ promising candidate major cause indicating preservation identify pathogen gut microbiota guided anti gastric diseases fusion analysis bond occupancy 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 (<i>r</i> = −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. 2026-09-29T00:00:00Z Text Journal contribution 10.1021/acsomega.6c05087.s001 https://figshare.com/articles/journal_contribution/Integrated_In_Silico_Analysis_Reveals_ABC_Transporter_ATP-Binding_Protein_as_a_Therapeutic_Target_in_Helicobacter_pylori/34028580 CC BY-NC 4.0