The effect of Li+ on GSK-3 inhibition: Molecular dynamics simulation

Glycogen synthase kinase-3 (GSK-3) is a kind of serine-threonine protein kinase. It places important roles in several signaling pathways and it is a key therapeutic target for a number of diseases, such as diabetes, cancer, Alzheimer’s disease and chronic inflammation. Mg2+ ions which interact with ATP are conserved in GSK. They are important in phosphoryl transfer. Li+ is an inhibitor for GSK-3. It is used to treat bipolar mood disorder. This paper illustrates the effect of Li+ on GSK-3. When MgI2+ is replaced by Li+, the atom fluctuation of GSK-3 will rise, and the in-line phosphoryl transfer mechanism is probably demolished and the binding of pre-phosphorylated substrates may be disturbed. All the results we obtained clearly suggest that inhibition to GSK-3 is caused by the MgI2+ replacement with Li+.