Atomistic simulations reveal impacts of missense mutations on the structure and function of SynGAP1.

ABSTRACT: De novo mutations in the synaptic GTPase activating protein (SynGAP) are associated with neurological disorders like intellectual disability, epilepsy, and autism. SynGAP is also implicated in Alzheimer's disease and cancer. Although pathogenic variants are highly penetrant in neurodevelopmental conditions, a substantial number of them are caused by missense mutations that are difficult to diagnose. Hence, in silico mutagenesis was performed for probing the missense effects within the N-terminal region of SynGAP structure. Through extensive molecular dynamics simulations, encompassing three 150-ns replicates for 211 variants, the impact of missense mutations on the protein fold was assessed. The effect of the mutations on the folding stability was also quantitatively assessed using free en

SUBMITTER: Ali AE 

PROVIDER: S-EPMC11418247 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature