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In TTR\u2010associated amyloidosis, amyloid fibrils form via destabilization of the tetramer into dimers and monomers. While many TTR mutations have been studied, the atomistic impact of multiple mutations on amyloid transthyretin (ATTR) self\u2010assembly remains underexplored. To the best of our knowledge, this is the first computational analysis reporting the impact of the L110M mutation on ATTR peptide aggregation. Using triplicate 1\u2009\u03bcs all\u2010atom molecular dynamics (MD) simulations, totaling 18\u2009\u03bcs, the conformational dynamics of cross\u2010\u03b2 amyloid fibrils in the ATTR(105\u2013115) segment were examined for both wild\u2010type and L110M mutant TTR. The L110M mutation consistently enhanced the \u03b2\u2010sheet content in all oligomers, with increases of ~1%, ~5%, and ~4% over the wild\u2010type in the 2\u2010, 4\u2010, and 8\u2010peptide systems, respectively. Molecular mechanics Poisson\u2013Boltzmann surface area (MM\u2010PBSA) calculations revealed higher effective binding free energy for the L110M mutant, with residue M110 contributing significantly to stabilization. These results suggest that L110M modestly enhances conformational order and stability in the TTR peptide assemblies without major structural disruption, deepening our understanding of amyloidogenesis in TTR\u2010related disorders.<\/jats:p>","DOI":"10.1002\/prot.70046","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T08:56:36Z","timestamp":1756976196000},"page":"570-581","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effect of\n                    <scp>L110M<\/scp>\n                    Mutation on the Structure and Stability of\n                    <scp>ATTR<\/scp>\n                    (105\u2013115) Peptide Assembly: A Computational Study"],"prefix":"10.1002","volume":"94","author":[{"given":"Prabuddha","family":"Bhattacharya","sequence":"first","affiliation":[{"name":"Department of Chemistry Mrinalini Datta Mahavidyapith  Kolkata 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