title: Quantum mechanical calculation of electric fields and vibrational Stark shifts at active site of human aldose reductase.
abstract: Recent advance in biophysics has made it possible to directly measure site-specific electric field at internal sites of proteins using molecular probes with C = O or C≡N groups in the context of vibrational Stark effect. These measurements directly probe changes of electric field at specific protein sites due to, e.g., mutation and are very useful in protein design. Computational simulation of the Stark effect based on force fields such as AMBER and OPLS, while providing good insight, shows large errors in comparison to experimental measurement due to inherent difficulties associated with point charge based representation of force fields. In this study, quantum mechanical calculation of protein's internal electrostatic properties and vibrational Stark shifts was carried out by using electrostatically embedded generalized molecular fractionation with conjugate caps method. Quantum calculated change of mutation-induced electric field and vibrational Stark shift is reported at the internal probing site of enzyme human aldose reductase. The quantum result is in much better agreement with experimental data than those predicted by force fields, underscoring the deficiency of traditional point charge models describing intra-protein electrostatic properties.
authors.affiliation: Center for Optics and Optoelectronics Research, College of Science, Zhejiang University of Technology, Hangzhou, Zhejiang 310023, China.
authors.forename: Xianwei
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Precision Spectroscopy, Institute of Theoretical and Computational Science, East China Normal University, Shanghai 200062, China.
authors.forename: John Z H
authors.initials: JZ
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Precision Spectroscopy, Institute of Theoretical and Computational Science, East China Normal University, Shanghai 200062, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: He
mesh_terms: D000449:Aldehyde Reductase / Q000737:chemistry* / Q000378:metabolism; D020134:Catalytic Domain; D006801:Humans; D011789:Quantum Theory; D055672:Static Electricity; D014732:Vibration
chemical_list: D000449:Aldehyde Reductase