{
  "abstract": "Rescoring docked ligands with molecular dynamics (MD) and end point free energy methods such as MM/GBSA is widely used, but its benefit over docking for series of close analogs is uncertain. We compared AutoDock Vina scores with Md based MM/GBSA energies for 29 neutral p38 kinase inhibitors (PDB 3FLY) from the Open Force Field protein-ligand benchmark, whose IC50 values from a single publication span 3.8 kcal/mol in estimate {Delta}G. Each ligand was docked with three random seeds and simulated in two independent 20 ns replicas started from the benchmark pose (AMBER99SB-ILDN, GAFF2, TIP3L; GROMACS). MM/GBSA energies were calculated from 251 frames per trajectory without an entropy term. All 58 simulations remained stable with the ligand bound. Vina scores correlated weakly with experimental {Delta}G (Spearman {rho} = 0.28 98% CI -0.15 to 0.62), as did replica averaged MM/GBSA energies ({rho} = 0.24 -0.18 to 0.62). The difference was -0.03 (-0.50 to 0.43), so the methods were not distinguishable. Independent replicas of the same ligand differed by 3.3 kcal/mol on average, comparable to the experimental range. Raising the interior dielectric constant from 1 to 2 gave a nearly identical ranking ({rho} = 0.96 between the two sets of scores; {rho} = 0.37 against experiment, -0.04 to 0.69). In an exploratory analysis, ligands size alone correlated with affinity ({rho} = 0.60, 0.28 to 0.82), whereas neither computed score tracked size. For this narrow range series, short MD rescoring gave no measurable improvement over docking, and replica variability limited its resolution.",
  "abstract_shown": true,
  "affiliations": [
    "St.Xavier's College"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "A. Dhakal"
    },
    {
      "name": "G. Chand"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/erq0dtckpacg0.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.27.762277",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762277v1.full",
  "id": "erq0dtckpacg0",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762277v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biophysics"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762277v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-27",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/erq0dtckpacg0.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:21:20Z",
      "native_id": "10.64898/2026.10.27.762277",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762277v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "Does Short Molecular Dynamics Rescoring Improve the Ranking of p38α Inhibitors over Docking? A Replicate Benchmark",
  "title_text": "Does Short Molecular Dynamics Rescoring Improve the Ranking of p38α Inhibitors over Docking? A Replicate Benchmark",
  "type": "preprint",
  "updated_at": "2026-11-01T00:21:15Z",
  "url": "https://research.draconitic.com/paper/erq0dtckpacg0",
  "venue": "bioRxiv",
  "versions": []
}