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Title: Quantum mechanical calculation of electric fields and vibrational Stark shifts at active site of human aldose reductase

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:
 [1] ;  [2] ; ;  [3] ;  [2]
  1. Center for Optics and Optoelectronics Research, College of Science, Zhejiang University of Technology, Hangzhou, Zhejiang 310023 (China)
  2. (China)
  3. State Key Laboratory of Precision Spectroscopy, Institute of Theoretical and Computational Science, East China Normal University, Shanghai 200062 (China)
Publication Date:
OSTI Identifier:
22493214
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Chemical Physics; Journal Volume: 143; Journal Issue: 18; Other Information: (c) 2015 AIP Publishing LLC; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL CHEMISTRY; AMBER; BIOPHYSICS; CARBON; COMPARATIVE EVALUATIONS; ELECTRIC FIELDS; ENZYMES; FRACTIONATION; HUMAN POPULATIONS; MUTATIONS; OXYGEN; POINT CHARGE; PROBES; QUANTUM MECHANICS; STARK EFFECT