Structural insight into receptor-selectivity for lurasidone

► Structural models of lurasidone-GPCRs were constructed by in silico study. ► We elucidated structural features that gave lurasidone high receptor selectivity. ► We revealed structural features that differentiate lurasidone from other drugs. ► Structural insight was validated by the binding experiment of novel derivatives. ► Our protocols would realize virtual screening and SBDD for novel CNS drugs.