Contact-Map-Driven Exploration of Heterogeneous Protein-Folding Paths
Ziad Fakhoury, Gabriele C. Sosso, Scott Habershon
TL;DR
This paper introduces a new method for exploring different protein-folding paths using contact maps, improving accuracy and reliability compared to previous approaches.
Contribution
The paper introduces a topologically informed metric, a reformulated folding path generation, and a new structural back-mapping algorithm for heterogeneous protein-folding paths.
Findings
The enhanced contact-map-based strategy reliably generates structurally sound folding intermediates.
The method successfully identifies alternative folding mechanisms of a multifolding-pathway protein.
The approach outperforms previous strategies by reducing irrelevant intermediates and aligning with molecular dynamics results.
Abstract
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 nontrivial compact native structure along distinct pathways defined by…
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Taxonomy
TopicsBiochemical and Structural Characterization · Protein Structure and Dynamics · Force Microscopy Techniques and Applications