{"paper":{"title":"An Efficient Approach for Calculating Free Energy in Molecular Dynamics: Demineralization of Hydroxyapatite as a Case Study","license":"http://creativecommons.org/licenses/by-nc-nd/4.0/","headline":"An adaptive method mixes expensive high-quality free energy runs with cheap low-quality ones to profile hydroxyapatite demineralization at far lower total cost.","cross_cats":[],"primary_cat":"cond-mat.mtrl-sci","authors_text":"Alexander M. Korsunsky, Jin-Chong Tan, Mahdi Tavakol","submitted_at":"2026-05-16T12:18:08Z","abstract_excerpt":"Despite the strength of Molecular Dynamics simulations in providing insights into the microscopic details of phenomenon in many fields in materials science, physics and biology, the biggest barrier is its limited timescale which is several orders of magnitude lower than the timescale of the real-world processes and phenomena being modeled. Free energy calculations are designed as a remedy to this problem that in theory can overcome this barrier. This is particularly relevant for biomineralisation processes such as tooth mineral formation and dissolution, while reflecting a broader challenge in"},"claims":{"count":4,"items":[{"kind":"strongest_claim","text":"We designed a new adaptive free energy calculation methodology which combines high quality, high computational cost free energy values with lower quality, lower cost values to build up the entire free energy profile. In the best case scenario this method lowers manifold the computational cost required for the non-equilibrium work free energy calculations compared to both the regular method and the reversible simulation.","source":"verdict.strongest_claim","status":"machine_extracted","claim_id":"C1","attestation":"unclaimed"},{"kind":"weakest_assumption","text":"The assumption that a small number of high-quality reversible pulling simulations (each taking 75 days) provide an accurate ground-truth free energy profile against which the adaptive combination of mixed-quality runs can be reliably validated, and that differences in initial structure equilibration dominate over the number of independent trajectories.","source":"verdict.weakest_assumption","status":"machine_extracted","claim_id":"C2","attestation":"unclaimed"},{"kind":"one_line_summary","text":"The authors propose an adaptive non-equilibrium work method for free energy profiles in MD that combines high- and low-quality simulations to cut computational cost while matching results from long reversible reference runs, shown on hydroxyapatite demineralization.","source":"verdict.one_line_summary","status":"machine_extracted","claim_id":"C3","attestation":"unclaimed"},{"kind":"headline","text":"An adaptive method mixes expensive high-quality free energy runs with cheap low-quality ones to profile hydroxyapatite demineralization at far lower total cost.","source":"verdict.pith_extraction.headline","status":"machine_extracted","claim_id":"C4","attestation":"unclaimed"}],"snapshot_sha256":"ab718bd412f565b174ab84cb3f3aae0808e20ffb56168198336b0ccc8b354469"},"source":{"id":"2605.16957","kind":"arxiv","version":1},"verdict":{"id":"aeb94703-7471-48f5-a960-9484729602ae","model_set":{"reader":"grok-4.3"},"created_at":"2026-05-19T20:32:35.177055Z","strongest_claim":"We designed a new adaptive free energy calculation methodology which combines high quality, high computational cost free energy values with lower quality, lower cost values to build up the entire free energy profile. In the best case scenario this method lowers manifold the computational cost required for the non-equilibrium work free energy calculations compared to both the regular method and the reversible simulation.","one_line_summary":"The authors propose an adaptive non-equilibrium work method for free energy profiles in MD that combines high- and low-quality simulations to cut computational cost while matching results from long reversible reference runs, shown on hydroxyapatite demineralization.","pipeline_version":"pith-pipeline@v0.9.0","weakest_assumption":"The assumption that a small number of high-quality reversible pulling simulations (each taking 75 days) provide an accurate ground-truth free energy profile against which the adaptive combination of mixed-quality runs can be reliably validated, and that differences in initial structure equilibration dominate over the number of independent trajectories.","pith_extraction_headline":"An adaptive method mixes expensive high-quality free energy runs with cheap low-quality ones to profile hydroxyapatite demineralization at far lower total cost."},"integrity":{"clean":true,"summary":{"advisory":0,"critical":0,"by_detector":{},"informational":0},"endpoint":"/pith/2605.16957/integrity.json","findings":[],"available":true,"detectors_run":[{"name":"doi_title_agreement","ran_at":"2026-05-19T21:01:19.085102Z","status":"completed","version":"1.0.0","findings_count":0},{"name":"doi_compliance","ran_at":"2026-05-19T20:40:51.688915Z","status":"completed","version":"1.0.0","findings_count":0},{"name":"cited_work_retraction","ran_at":"2026-05-19T19:51:58.556879Z","status":"completed","version":"1.0.0","findings_count":0},{"name":"claim_evidence","ran_at":"2026-05-19T18:41:56.233556Z","status":"completed","version":"1.0.0","findings_count":0},{"name":"ai_meta_artifact","ran_at":"2026-05-19T18:33:26.318171Z","status":"skipped","version":"1.0.0","findings_count":0}],"snapshot_sha256":"9645fa34ee14259ce9d3209aeec34c42134c3f64876a3b4b53501a05b495e1f5"},"references":{"count":4,"sample":[{"doi":"","year":1997,"title":"Because such rare events underlie critical molecular phenomena, the ability to compute accurate free energy differences and profiles is of vital importance. At the conceptual level, the importance of ","work_id":"6063bc49-418c-4376-9a93-6beda15e12f9","ref_index":1,"cited_arxiv_id":"","is_internal_anchor":false},{"doi":"10.5281/zenodo.22558","year":null,"title":"University of Oxford Advanced Research Computing Facility","work_id":"2026374c-f422-4339-8ec9-d2266e44cdf5","ref_index":2,"cited_arxiv_id":"","is_internal_anchor":false},{"doi":"","year":1957,"title":"References (1) Alder, B. J.; Wainwright, T. E. Phase Transition for a Hard Sphere System. J. Chem. Phys. 1957, 27 (5), 1208–1209. 17 (2) Mi, F.; He, Z.; Jiang, G.; Ning, F. 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