Periplasmic　binding　protein-dependent　maltose　transport　system　(MBP-MalFGK(2))　of　Escherichia　coli,　an　important　member　of　the　Adenosine　triphosphate-binding　cassette　transporter　superfamily,　is　in　charge　of　the　transportation　of　maltoses　across　cellular　membrane.　Studies　have　shown　that　this　transport　processes　are　activated　by　the　binding　of　maltose　and　are　accompanied　by　large-scale　cooperative　movements　between　different　domains　which　are　mediated　by　a　network　of　important　residues　related　to　signal　transduction　and　allosteric　regulation.　In　this　paper,　the　functionally　crucial　residues　and　long-range　allosteric　pathway　of　the　regulation　of　the　system　by　substrate　were　identified　by　utilising　a　coarse-grained　thermodynamic　method　proposed　by　our　group.　The　residues　whose　perturbations　markedly　change　the　binding　free　energy　between　maltoses　and　MBP-MalFGK(2)　were　considered　to　be　key　residues.　In　result,　the　key　residues　in　62　clusters　distributed　in　different　subdomains　were　identified　successfully,　and　the　results　from　our　calculation　are　highly　consistent　with　experimental　and　theoretical　observations.　Furthermore,　we　explored　the　long-range　cooperation　within　the　transporter.　These　studies　will　help　us　better　understand　the　physical　mechanism　of　the　effects　of　the　maltose　on　MBP-MalFGK(2)　by　long-range　allosteric　modulation.　[GRAPHICS]　.