Toward molecular models of proton pumping:Challenges,methods and relevant applications  

作　　者：RICCARDI Demian GOYAL Puja 

机构地区：[1]Department of Chemistry and Theoretical Chemistry Institute,University of Wisconsin

出　　处：《Science China Chemistry》2012年第1期3-18,共16页中国科学（化学英文版）

基　　金：supported in part by NIH grant R01-GM084028;NSF grant CHE-0957285;U.S.Department of Energy Genomics:GTL and Sci-DAC Programs (DEFG02-04ER25627);supported in part by the National Science Foundation through a major instrumentation grant (CHE-0840494)

摘　　要：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.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.

关 键 词：proton pumping QM/MM simulations SCC-DFTB microscopic pKa multi-scale simulations 

分 类 号：O641[理学—物理化学]