scholarly journals Testing the Limitations of MD-Based Local Electric Fields Using the Vibrational Stark Effect in Solution: Penicillin G as a Test Case

2021 ◽  
Author(s):  
Jacek Kozuch ◽  
Samuel H. Schneider ◽  
Chu Zheng ◽  
Zhe Ji ◽  
Richard T. Bradshaw ◽  
...  
Keyword(s):  
Electric Fields ◽  
Stark Effect ◽  
Penicillin G ◽  
Test Case

scholarly journals Testing the Limitations of MD-based Local Electric Fields Using the Vibrational Stark Effect in Solution: Penicillin G as a Test Case

2021 ◽  
Author(s):  
Jacek Kozuch ◽  
Samuel Schneider ◽  
Chu Zheng ◽  
Zhe Ji ◽  
Richard T Bradshaw ◽  
...  
Keyword(s):  
Electric Fields ◽  
Active Sites ◽  
Stark Effect ◽  
Force Fields ◽  
Direct Method ◽  
Md Simulations ◽  
Penicillin G ◽  
Conformational Sampling ◽  
Test Case ◽  
Water Models

<div>Non-covalent interactions underlie nearly all molecular processes in the condensed phase from solvation to</div><div>catalysis. Their quantification within a physically consistent framework remains challenging. Experimental vibrational Stark effect (VSE)-based solvatochromism can be combined with molecular dynamics (MD) simulations to quantify the electrostatic forces in solute-solvent interactions for small rigid molecules and, by extension, when these solutes bind in enzyme active sites. While generalizing this approach towards more complex (bio)molecules, such as the conformationally flexible and charged penicillin G (PenG), we were surprised to observe inconsistencies in MD-based electric fields. Combining synthesis, VSE spectroscopy, and computational methods, we provide an intimate view on the origins of these discrepancies. We observe that the electrics fields are correlated to conformation-dependent effects of the flexible PenG side-chain, including both local solvation structure and solute conformational sampling in MD. Additionally, we identified that MD-based electric fields are consistently overestimated in 3-point water models in the vicinity of charged groups; this cannot be entirely ameliorated using polarizable force fields (AMOEBA) or advanced water models. This work demonstrates the value of the VSE as a direct method for experiment-guided refinements of MD force fields and establishes a general reductionist approach to calibrating vibrational probes for complex (bio)molecules.</div>

scholarly journals Testing the Limitations of MD-based Local Electric Fields Using the Vibrational Stark Effect in Solution: Penicillin G as a Test Case

2021 ◽  
Author(s):  
Jacek Kozuch ◽  
Samuel Schneider ◽  
Chu Zheng ◽  
Zhe Ji ◽  
Richard T Bradshaw ◽  
...  
Keyword(s):  
Electric Fields ◽  
Active Sites ◽  
Stark Effect ◽  
Force Fields ◽  
Direct Method ◽  
Md Simulations ◽  
Penicillin G ◽  
Conformational Sampling ◽  
Test Case ◽  
Water Models

<div>Non-covalent interactions underlie nearly all molecular processes in the condensed phase from solvation to</div><div>catalysis. Their quantification within a physically consistent framework remains challenging. Experimental vibrational Stark effect (VSE)-based solvatochromism can be combined with molecular dynamics (MD) simulations to quantify the electrostatic forces in solute-solvent interactions for small rigid molecules and, by extension, when these solutes bind in enzyme active sites. While generalizing this approach towards more complex (bio)molecules, such as the conformationally flexible and charged penicillin G (PenG), we were surprised to observe inconsistencies in MD-based electric fields. Combining synthesis, VSE spectroscopy, and computational methods, we provide an intimate view on the origins of these discrepancies. We observe that the electrics fields are correlated to conformation-dependent effects of the flexible PenG side-chain, including both local solvation structure and solute conformational sampling in MD. Additionally, we identified that MD-based electric fields are consistently overestimated in 3-point water models in the vicinity of charged groups; this cannot be entirely ameliorated using polarizable force fields (AMOEBA) or advanced water models. This work demonstrates the value of the VSE as a direct method for experiment-guided refinements of MD force fields and establishes a general reductionist approach to calibrating vibrational probes for complex (bio)molecules.</div>

scholarly journals The Interplay of Electrostatics and Chemical Positioning in the Evolution of Antibiotic Resistance in TEM β-Lactamases

2021 ◽  
Author(s):  
Samuel H Schneider ◽  
Jacek Kozuch ◽  
Steven G Boxer
Keyword(s):  
Antibiotic Resistance ◽  
Electric Fields ◽  
Stark Effect ◽  
Structural Changes ◽  
Fitness Landscape ◽  
Md Simulations ◽  
Penicillin G ◽  
Modulate Function ◽  
Evolutionary Trajectory ◽  
Enzyme Active Site

The interplay of enzyme active site electrostatics and chemical positioning are important for understanding the origin(s) of enzyme catalysis and the design of novel catalysts. We reconstruct the evolutionary trajectory of TEM-1 β-lactamase to TEM-52 towards extended-spectrum activity to better understand the emergence of antibiotic resistance and to provide insights into the structure-function paradigm and non-covalent interactions involved in catalysis. Utilizing a detailed kinetic analysis and the vibrational Stark effect, we quantify the changes in rate and electric fields in the Michaelis and acyl-enzyme complexes for penicillin G and cefotaxime to ascertain the evolutionary role of electric fields to modulate function. These data are combined with MD simulations to interpret and quantify the substrate-dependent structural changes during evolution. We observe that evolution utilizes a large preorganized electric field and substrate-dependent chemical positioning to facilitate catalysis. This governs the evolvability, substrate promiscuity, and protein fitness landscape in TEM β-lactamase antibiotic resistance.

scholarly journals Piezoelectric Level Splitting in GaInN/GaN Quantum Wells

1999 ◽  
Vol 4 (S1) ◽  
pp. 357-362
Author(s):  
C. Wetzel ◽  
T. Takeuchi ◽  
H. Amano ◽  
I. Akasaki
Keyword(s):  
Quantum Wells ◽  
Electric Fields ◽  
High Performance ◽  
Stark Effect ◽  
Electronic Band Structure ◽  
Multiple Quantum Well ◽  
Multiple Quantum ◽  
Large Set ◽  
Electronic Band ◽  
Level Splitting

Identification of the electronic band structure in AlInGaN heterostructures is the key issue in high performance light emitter and switching devices. In device-typical GaInN/GaN multiple quantum well samples in a large set of variable composition a clear correspondence of transitions in photo- and electroreflection, as well as photoluminescence is found. The effective band offset across the GaN/GaInN/GaN piezoelectric heterointerface is identified and electric fields from 0.23 - 0.90 MV/cm are directly derived. In the bias voltage dependence a level splitting within the well is observed accompanied by the quantum confined Stark effect. We furthermore find direct correspondence of luminescence bands with reflectance features. This indicates the dominating role of piezoelectric fields in the bandstructure of such typical strained layers.

scholarly journals Piezoelectric Level Splitting in GaInN/GaN Quantum Wells

1998 ◽  
Vol 537 ◽  
Author(s):  
C. Wetzel ◽  
T. Takeuchi ◽  
H. Amano ◽  
I. Akasaki
Keyword(s):  
Quantum Wells ◽  
Electric Fields ◽  
High Performance ◽  
Stark Effect ◽  
Electronic Band Structure ◽  
Multiple Quantum Well ◽  
Multiple Quantum ◽  
Large Set ◽  
Electronic Band ◽  
Level Splitting

AbstractIdentification of the electronic band structure in AlInGaN heterostructures is the key issue in high performance light emitter and switching devices. In device-typical GaInN/GaN multiple quantum well samples in a large set of variable composition a clear correspondence of transitions in photo- and electroreflection, as well as photoluminescence is found. The effective band offset across the GaN/GaInN/GaN piezoelectric heterointerface is identified and electric fields from 0.23 - 0.90 MV/cm are directly derived. In the bias voltage dependence a level splitting within the well is observed accompanied by the quantum confined Stark effect. We furthermore find direct correspondence of luminescence bands with reflectance features. This indicates the dominating role of piezoelectric fields in the bandstructure of such typical strained layers.

scholarly journals Supramolecular Stark Effect in Host-Guest Complexes via Charge Density Analysis

2014 ◽  
Vol 70 (a1) ◽  
pp. C674-C674
Author(s):  
Sajesh Thomas ◽  
Rebecca Fuller ◽  
Alexandre Sobolev ◽  
Philip Schauer ◽  
Simon Grabowsky ◽  
...  
Keyword(s):  
Electric Field ◽  
Charge Density ◽  
Electric Fields ◽  
Active Sites ◽  
Stark Effect ◽  
Dipole Moments ◽  
Covalent Bonds ◽  
Guest Molecules ◽  
Density Mapping ◽  
Density Analysis

The effect of an electric field on the vibrational spectra, the Vibrational Stark Effect (VSE), has been utilized extensively to probe the local electric field in the active sites of enzymes [1, 2]. For this reason, the electric field and consequent polarization effects induced by a supramolecular host system upon its guest molecules attain special interest due to the implications for various biological processes. Although the host-guest chemistry of crown ether complexes and clathrates is of fundamental importance in supramolecular chemistry, many of these multicomponent systems have yet to be explored in detail using modern techniques [3]. In this direction, the electrostatic features associated with the host-guest interactions in the inclusion complexes of halogenated acetonitriles and formamide with 18-crown-6 host molecules have been analyzed in terms of their experimental charge density distribution. The charge density models provide estimates of the molecular dipole moment enhancements which correlate with the simulated values of dipole moments under electric field. The accurate electron density mapping using the multipole formalism also enable the estimation of the electric field experienced by the guest molecules. The electric field vectors thus obtained were utilized to estimate the vibrational stark effect in the nitrile (-C≡N) and carbonyl (C=O) stretching frequencies of the guest molecules via quantum chemical calculations in gas phase. The results of these calculations indicate remarkable elongation of C≡N and C=O bonds due to the electric fields. The electronic polarization in these covalent bonds induced by the field manifests as notable red shifts in their characteristic vibrational frequencies. These results derived from the charge densities are further supported by FT-IR experiments and thus establish the significance of a phenomenon that could be termed as the "supramolecular Stark effect" in crystal environment.

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