GoLoco motif proteins binding to Gαi1: insights from molecular simulations

Molecular dynamics simulations, computational alanine scanning and sequence analysis were used to investigate the structural properties of the G alpha(i1)/GoLoco peptide complex. Using these methodologies, binding of the GoLoco motif peptide to the G alpha(i1) subunit was found to restrict the relative movement of the helical and catalytic domains in the G alpha(i1) subunit, which is in agreement with a proposed mechanism of GDP dissociation inhibition by GoLoco motif proteins. In addition, the results provide further insights into the role of the Switch IV region located within the helical domain of G alpha, the conformation of which might be important for interactions with various G alpha partners.