Unraveling the Behavior of Intrinsically Disordered Protein c-Myc: A Study Utilizing Gaussian-Accelerated Molecular Dynamics.

ABSTRACT: The protein c-Myc is a transcription factor that remains largely intrinsically disordered and is known to be involved in various biological processes and is overexpressed in various cancers, making it an attractive drug target. However, intrinsically disordered proteins such as c-Myc do not show funnel-like basins in their free-energy landscapes; this makes their druggability a challenge. For the first time, we propose a heterodimer model of c-Myc/Max in full length in this work. We used Gaussian-accelerated molecular dynamics (GaMD) simulations to explore the behavior of c-Myc and its various regions, including the transactivation domain (TAD) and the basic helix-loop-helix-leucine-zipper (bHLH-Zipper) motif in three different conformational states: (a) monomeric c-Myc, (b) c-Myc when bou

SUBMITTER: Gunasinghe KKJ 

PROVIDER: S-EPMC10795134 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature