▁the ▁substr ate ▁itself ▁( hom otrop ic ▁effect ors ) ▁or ▁some ▁other ▁small ▁mole c ule ▁( h eter otrop ic ▁effect or ), ▁may ▁cause ▁the ▁en zym e ▁to ▁become ▁more ▁active ▁or ▁less ▁active ▁by ▁red ist rib uting ▁the ▁ensemble ▁between ▁the ▁higher ▁aff inity ▁and ▁lower ▁aff inity ▁states . ▁The ▁binding ▁sites ▁for ▁heter otrop ic ▁effect ors , ▁called ▁al loster ic ▁sites , ▁are ▁usually ▁separate ▁from ▁the ▁active ▁site ▁yet ▁therm od ynam ically ▁couple d . ▁Al loster ic ▁Database ▁( AS D , ▁http :// md l . sh s mu . edu . cn / AS D ) ▁ ▁provides ▁a ▁central ▁resource ▁for ▁the ▁display , ▁search ▁and ▁analysis ▁of ▁the ▁structure , ▁function ▁and ▁related ▁annotation ▁for ▁al loster ic ▁mole cules , ▁including ▁al loster ic ▁en zym es ▁and ▁their ▁mod ul ators . ▁Each ▁en zym e ▁is ▁annot ated ▁with ▁detailed ▁description ▁of ▁al lost ery , ▁bi ological ▁process ▁and ▁related ▁dise ases , ▁and ▁each ▁mod ulator ▁with ▁binding ▁aff inity , ▁phys ico chem ical ▁properties ▁and ▁th era pe ut ic ▁area . ▁ ▁Kin etic ▁properties ▁ ▁Hem og lo bin , ▁though ▁not ▁an ▁en zym e , ▁is ▁the ▁canonical ▁example ▁of ▁an ▁al loster ic ▁protein ▁mole c ule ▁- ▁and ▁one ▁of ▁the ▁earliest ▁to ▁have ▁its ▁cry stal ▁structure ▁solved ▁( by ▁Max ▁Per utz ). ▁ ▁More ▁recently , ▁the ▁E .