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

• Published in: Science China. Chemistry Vol. 55; no. 1; pp. 3 - 18
• Main Authors: Riccardi, Demian, Zhu, Xiao, Goyal, Puja, Yang, Shuo, Hou, GuanHua, Cui, Qiang
• Format: Journal Article
• Language: English
• Published: Heidelberg SP Science China Press 2012; Springer Nature B.V
• Subjects: Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Density functional theory; Hamiltonian functions; Proteins; Protons; Pumps; Quantum mechanics; Reviews; 分子模型; 密度泛函理论; 应用; 机械问题; 生物分子; 质子泵; 跨膜蛋白; 远距离运输; QM/MM simulations; microscopic p; proton pumping; SCC-DFTB; multi-scale simulations
• ISSN: 1674-7291; 1869-1870
• DOI: 10.1007/s11426-011-4458-9

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.