Reconstruction of ARNT PAS-B Unfolding Pathways by Steered Molecular Dynamics and Artificial Neural Networks.

ABSTRACT: Several experimental studies indicated that large conformational changes, including partial domain unfolding, have a role in the functional mechanisms of the basic helix loop helix Per/ARNT/SIM (bHLH-PAS) transcription factors. Recently, single-molecule atomic force microscopy (AFM) revealed two distinct pathways for the mechanical unfolding of the ARNT PAS-B. In this work we used steered molecular dynamics simulations to gain new insights into this process at an atomistic level. To reconstruct and classify pathways sampled in multiple simulations, we designed an original approach based on the use of self-organizing maps (SOMs). This led us to identify two types of unfolding pathways for the ARNT PAS-B, which are in good agreement with the AFM findings. Analysis of average forces mapped on

SUBMITTER: Motta S 

PROVIDER: S-EPMC8047803 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature