Molecular Dynamics Simulations of the SPRED2^Leu100Pro EVH-1 Domain Complexed with the GAP-Related Domain of Neurofibromin.

ABSTRACT: The homozygous Leu100Pro amino acid substitution in SPRED2, a protein negatively controlling RAS function, has recently been identified to be causally linked to a recessive form of Noonan syndrome. The amino acid substitution was documented to affect protein stability and cause a decreased and/or less stable interaction with neurofibromin, a RAS-specific GTPase activating protein negatively regulating RAS function. To further investigate the structural and functional impact of Leu100Pro, we structurally characterized the consequences of this change on the interaction of SPRED2 with neurofibromin, by 1 µn-long molecular dynamics (MD) simulations. Our analyses failed in identifying local perturbations predicted to disrupt or dramatically affect SPRED2 binding to neurofibromin, though a rearr

SUBMITTER: Terrusa M 

PROVIDER: S-EPMC12072562 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature