Motivated by several long-lasting mechanistic questions for biomolecular proton pumps,we have engaged in developing hybrid quantum mechanical/molecular mechanical(QM/MM) methods that allow an efficient and reliable de...Motivated by several long-lasting mechanistic questions for biomolecular proton pumps,we have engaged in developing hybrid quantum mechanical/molecular mechanical(QM/MM) methods that allow an efficient and reliable description of long-range proton transport in transmembrane proteins.In this review,we briefly discuss several relevant issues:the need to develop a "multi-scale" generalized solvent boundary potential(GSBP) for the analysis of chemical events in large trans-membrane proteins,approaches to validate such a protocol,and the importance of improving the flexibility of QM/MM Hamiltonian.Several recent studies of model and realistic protein systems are also discussed to help put the discussions into context.Collectively,these studies suggest that the QM/MM-GSBP framework based on an approximate density functional theory(SCC-DFTB) as QM holds the promise to strike the proper balance between computational efficiency,accuracy and generality.With additional improvements in the methodology and recent developments by others,especially powerful sampling techniques,this "multi-scale" framework will be able to help unlock the secrets of proton pumps and other biomolecular machines.展开更多
文摘Motivated by several long-lasting mechanistic questions for biomolecular proton pumps,we have engaged in developing hybrid quantum mechanical/molecular mechanical(QM/MM) methods that allow an efficient and reliable description of long-range proton transport in transmembrane proteins.In this review,we briefly discuss several relevant issues:the need to develop a "multi-scale" generalized solvent boundary potential(GSBP) for the analysis of chemical events in large trans-membrane proteins,approaches to validate such a protocol,and the importance of improving the flexibility of QM/MM Hamiltonian.Several recent studies of model and realistic protein systems are also discussed to help put the discussions into context.Collectively,these studies suggest that the QM/MM-GSBP framework based on an approximate density functional theory(SCC-DFTB) as QM holds the promise to strike the proper balance between computational efficiency,accuracy and generality.With additional improvements in the methodology and recent developments by others,especially powerful sampling techniques,this "multi-scale" framework will be able to help unlock the secrets of proton pumps and other biomolecular machines.
