Predicting Pathways between Distant Configurations for Biomolecules.
Journal of chemical theory and computation
American Chemical Society (ACS)
MetadataShow full item record
Roeder, K., & Wales, D. (2018). Predicting Pathways between Distant Configurations for Biomolecules.. Journal of chemical theory and computation, 14 (8), 4271-4278. https://doi.org/10.1021/acs.jctc.8b00370
Many of the most interesting rearrangements associated with function and dysfunction of biomolecules involve complex, highly non-linear pathways. Predicting these convoluted changes in structure is an important research challenge, since knowledge of key intermediate conformations at an atomic level of detail has the potential to inform the design of novel therapeutic strategies with enhanced specificity. The identification of kinetically relevant pathways can be strongly dependent on the construction of a physically relevant initial pathway between specified endpoints, avoiding artefacts such as chain crossings. In this contribution we describe an enhanced interpolation procedure to characterise initial pathways for complex rearrangements of a histone tail, α-helix to β-sheet conversion for amyloid-β 17−42 , and egfr kinase activation. Complete connected initial pathways with relatively low overall barriers are obtained in each case using an enhanced quasi-continuous interpolation scheme. This approach will help to extend the complexity and time scales accessible to computer simulation.
Humans, Peptide Fragments, Histones, Protein Conformation, Protein Structure, Secondary, Algorithms, Models, Molecular, Computer Simulation, Amyloid beta-Peptides, ErbB Receptors
External DOI: https://doi.org/10.1021/acs.jctc.8b00370
This record's URL: https://www.repository.cam.ac.uk/handle/1810/284190
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/