We introduce a statistical and linear response theory of selective conduction in biological ion channels with multiple binding sites and possible point mutation. We derive an effective grand-canonical ensemble and generalized Einstein relations for the selectivity filter, assuming strongly coordinated ionic motion, and allowing for ionic Coulomb blockade. The theory agrees well with data from the KcsA K^{+} channel and a mutant. We show that the Eisenman relations for thermodynamic selectivity follow from the condition for fast conduction and find that maximum conduction requires the binding sites to be nearly identical.