title: Accurate Calculation of Electric Fields Inside Enzymes.
abstract: The specific electric field generated by a protease at its active site is considered as an important source of the catalytic power. Accurate calculation of electric field at the active site of an enzyme has both fundamental and practical importance. Measuring site-specific changes of electric field at internal sites of proteins due to, eg, mutation, has been realized by using molecular probes with CO or CN groups in the context of vibrational Stark effect. However, theoretical prediction of change in electric field inside a protein based on a conventional force field, such as AMBER or OPLS, is often inadequate. For such calculation, quantum chemical approach or quantum-based polarizable or polarized force field is highly preferable. Compared with the result from conventional force field, significant improvement is found in predicting experimentally measured mutation-induced electric field change using quantum-based methods, indicating that quantum effect such as polarization plays an important role in accurate description of electric field inside proteins. In comparison, the best theoretical prediction comes from fully quantum mechanical calculation in which both polarization and inter-residue charge transfer effects are included for accurate prediction of electrostatics in proteins.
authors: Center for Optics & Optoelectronics Research, College of Science, Zhejiang University of Technology, Hangzhou, Zhejiang, China; School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China.
authors: X
authors: X
authors: Wang
authors: School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China; NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai, China. Electronic address: xiaohe@phy.ecnu.edu.cn.
authors: X
authors: X
authors: He
authors: School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China; NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai, China; New York University, New York, NY, United States. Electronic address: zhzhang@phy.ecnu.edu.cn.
authors: J Z H
authors: JZ
authors: Zhang
mesh_terms: D000449:Aldehyde Reductase / Q000737:chemistry*; D000480:Alkynes; D019943:Amino Acid Substitution; D048588:Benzoxazines / Q000737:chemistry; D055162:Biocatalysis; D020134:Catalytic Domain; D003521:Cyclopropanes; D004583:Electrons; D054303:HIV Reverse Transcriptase / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D015335:Molecular Probes / Q000737:chemistry; D009570:Nitriles / Q000737:chemistry; D011789:Quantum Theory; D013057:Spectrum Analysis / Q000379:methods; D055672:Static Electricity; D013251:Steroid Isomerases / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; C512007:IDD743; D015335:Molecular Probes; D009570:Nitriles; C484670:AKR1B1 protein, human; D000449:Aldehyde Reductase; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D013251:Steroid Isomerases; C098320:efavirenz
keywords: Charge transfer effect; Electric field; Molecular fragmentation; Polarization effect; Stark shift