2026-10-10T19:15:51Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33888817 2026-09-17T11:51:40Z portal_1197 item_type_3 month_year_09_2026

Data for Contact-map-driven exploration of heterogeneous protein-folding paths Ziad Fakhoury (24687072) Gabriele C. Sosso (1304346) Scott Habershon (1263891) Protein folding Protein folding -- Mathematical models Proteins -- Conformation Proteins -- Structure Graph theory Computational complexity Migrated from ePrints We have recently shown how physically-realizable protein-folding pathways can be generated using directed walks in the space of inter-residue contact-maps; combined with a back-transformation to move from protein contact-maps to Cartesian coordinates, we have demonstrated how this approach can generate protein-folding trajectory ensembles without recourse to molecular dynamics. In this article, we demonstrate that this framework can be used to study a challenging protein-folding problem that is known to exhibit two different folding paths which were previously identified through molecular dynamics simulation at several different temperatures. From the viewpoint of protein-folding mechanism prediction, this particular problem is extremely challenging to address, specifically involving folding to an identical non-trivial compact native structure along distinct pathways defined by heterogeneous secondary structural elements. Here, we show how our previously-reported contact-map-based protein-folding strategy can be significantly enhanced to enable accurate and robust prediction of heterogeneous folding paths by: (i) introducing a novel topologically-informed metric for comparing two protein contact maps, (ii) reformulating our graph-represented folding path generation, and (iii) introducing a new and more reliable structural back-mapping algorithm. These changes improve the reliability of generating structurally-sound folding intermediates, and dramatically decrease the number of physically-irrelevant folding intermediates generated by our previous simulation strategy. Most importantly, we demonstrate how our enhanced folding algorithm can successfully identify the alternative folding mechanisms of a multi-folding-pathway protein, in line with direct molecular dynamics simulations. 2024-07-01T00:00:00Z Dataset Dataset 10.82444/warw.33888817.v1 https://figshare.com/articles/dataset/Data_for_Contact-map-driven_exploration_of_heterogeneous_protein-folding_paths/33888817 CC BY 4.0