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domains walls (DWs) of head-to-head/tail-to-tail (H-H/T-T) type in ferroelectric (FE) materials are of immense interest for a comprehensive understanding of the FE attributes as well as ...harnessing them for new applications. Our first principles calculation suggests that such DW formation in hafnium zirconium oxide (HZO) based FEs depends on the unique attributes of the HZO unit cell, such as polar-spacer segmentation. Cross pattern of the polar and spacer segments in two neighboring domains along the polarization direction (where polar segment of one domain aligns with the spacer segment of another) boosts the stability of such DWs. We further show that low density of oxygen vacancies at the metal-HZO interface and high work function of metal electrodes are conducive for T-T DW formation. On the other hand, high density of oxygen vacancy and low work function of metal electrode favor H-H DW formation. Polarization bound charges at the DW get screened when band bending from depolarization field accumulates holes (electrons) in T-T (H-H) DW. For a comprehensive understanding, we also investigate their FE nature and domain growth mechanism. Our analysis suggests that a minimum thickness criterion of domains has to be satisfied for the stability of H-H/T-T DW and switching of the domains through such DW formation.
Abstract
To understand and harness the physical mechanisms of ferroelectric hafnium zirconium oxide (HZO)‐based devices, there is a need for clear understanding of domain interactions, their ...dynamics, negative capacitance effects, and other multidomain characteristics. These crucial attributes depend on the coupling between neighboring domains quantified by the gradient energy coefficient (
g
). Furthermore, HZO has unique orientation‐dependent lateral multidomain configurations. To develop an in‐depth understanding of multidomain effects, there is a need for a thorough analysis of
g
. In this work, the energetics of multidomain configurations and domain growth mechanism corresponding to lateral domain walls (DWs) of HZO are analyzed and gradient energy coefficients are quantified using first‐principles density functional theory calculations. These results indicate that one lateral direction exhibits the following characteristics: i) DW is ultra‐sharp and domain growth occurs unit‐cell‐by‐unit‐cell, ii) the value of
g
is negative and in the order of 10
−12
V m
3
C
−1
, and iii)
g
reduces (increases) with compressive (tensile) strain. In contrast, in the other lateral direction, the following attributes are observed: i) DW is gradual and domain growth occurs in quanta of half‐unit‐cell, ii)
g
is positive and in the order of 10
−10
V m
3
C
−1
, and iii)
g
increases (reduces) with compressive (tensile) strain.
In this work, a single layer n-doped MoS2 and p-doped WTe2 based vertical heterojunction tunnel FET has been investigated through a well-organized quantum mechanical approach. The key outcome is the ...design criteria of the device for low subthreshold swing keeping its length as short as possible. Inter-coupled real space model Hamiltonian of the device is formed by introducing the coupling energy of the WTe2 valence band and the MoS2 conduction band in the overlap region. Here, MATLAB based self-consistent analysis is used to numerically solve the device by coupling Schrödinger and Poisson equations taking into account the plane dependence of permittivity in 2D transition metal dichalcogenide materials. For 15 nm channel overlap length and 15 nm gate extension length, a subthreshold slope of as low as 10 mV/decade has been obtained. For 20 nm channel overlap length, an ON current of 18 µA/μm has been obtained as well. The effect of the top gate extension, overlap length, and dielectric layer thickness over the ON and OFF state currents has been explained from the viewpoint of device physics. Thus, the framework presented will help designers to optimize the device for improved performance.
We present an in-depth study on the theoretical calculation of an optimum reaction coordinate as a linear or nonlinear combination of important collective variables (CVs) sampled from an ensemble of ...reactive transition paths for an intramolecular proton transfer reaction catalyzed by the enzyme human carbonic anhydrase (HCA) II. The linear models are optimized by likelihood maximization for a given number of CVs. The nonlinear models are based on an artificial neural network with the same number of CVs and optimized by minimizing the root-mean-square error in comparison to a training set of committor estimators generated for the given transition. The nonlinear reaction coordinate thus obtained yields the free energy of activation and rate constant as 9.46 kcal mol–1 and 1.25 × 106 s–1, respectively. These estimates are found to be in quantitative agreement with the known experimental results. We have also used an extended autoencoder model to show that a similar analysis can be carried out using a single CV only. The resultant free energies and kinetics of the reaction slightly overestimate the experimental data. The implications of these results are discussed using a detailed microkinetic scheme of the proton transfer reaction catalyzed by HCA II.
We present, for the first time, how transient changes in the coordination number of zinc ion affects the rate determining step in the enzyme human carbonic anhydrase (HCA) II. The latter involves an ...intramolecular proton transfer between a zinc-bound water and a distant histidine residue (His-64). In the absence of time-resolved experiments, results from classical and QM-MM molecular dynamics and transition path sampling simulations are presented. The catalytic zinc ion is found to be present in two possible coordination states; viz. a stable tetra-coordinated state, T and a less stable penta-coordinated state, P with tetrahedral and trigonal bipyramidal coordination geometries, respectively. A fast dynamical inter-conversion occurs between T and P due to reorganization of active site water molecules making the zinc ion more positively charged in state P. When initiated from different coordination environments, the most probable mechanism of proton transfer is found to be deprotonation of the equatorial water molecule from state P and transfer of the excess proton via a short path formed by hydrogen bonded network of active site water molecules. We estimate the rate constant of proton transfer as
from P and
from T. A quantitative match of estimated k
with the experimental value, (
) suggests that dynamics of Zn coordination triggers the rate determining proton transfer step in HCA II.
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Semi-empirical SCC-DFTB based QM modelling is reported for the active site of human carbonic anhydrase II (HCA II), an enzyme having a rate determining proton transfer reaction with a ...rate constant of 106 s−1. In view of known limitations of SCC-DFTB, a detailed bench-marking of the SCC-DFTB results has been carried out against higher order density functional based theories using reactivity and time averaged network connections of the active site, derived from geometry optimization and QM/MM MD simulations. Bond lengths in the first coordination shell of Zn(II) ion, estimated using SCC-DFTB, are found to agree well with known EXAFS data. Other successful predictions include different reactivity descriptors, distribution of water around Zn(II) ion at the active site up to a separation of 5 Å and the persistence of similar water network for the key proton transfer step.
The role of structure and dynamics of an enzyme has been investigated at three different stages of its function including the chemical event it catalyzes. A one-pot computational method has been ...designed for each of these stages on the basis of classical and/or quantum mechanical–molecular mechanical molecular dynamics and transition path sampling simulations. For a pair of initial and final states A and B separated by a high free-energy barrier, using a two-stage selection process, several collective variables (CVs) are identified that can delineate A and B. However, these CVs are found to exhibit strong cross-coupling over the transition paths. A set of mutually orthogonal order parameters is then derived from these CVs and an optimal reaction coordinate, r, determined applying half-trajectory likelihood maximization along with a Bayesian information criterion. The transition paths are also used to project the multidimensional free energy surface and barrier crossing dynamics along r. The proposed scheme has been applied to the rate-determining intramolecular proton transfer reaction of the well-known enzyme human carbonic anhydrase II. The potential of mean force, F(r), in the absence of the chemical step is found to reproduce earlier results on the equilibrium population of two side-chain orientations of key residue His-64. Estimation of rate constants, k, from mean first passage times for the three different stages of catalysis shows that the rate-determining step of intramolecular proton transfer occurs with k ≃ 1.0 × 106 s–1, in close agreement with known experimental results.
The choice of suitable collective variables in formulating an optimal reaction coordinate is a challenging task for activated transitions between a pair of stable states especially when dealing with ...biochemical changes such as enzyme catalyzed reactions. A detailed benchmarking study is carried out on the choice of collective variables that can distinguish between the stable states unambiguously. We specifically address the issue if these variables may be directly used to model the optimal reaction coordinate, or if it would be better to use their orthogonalized counterparts. The proposed computational scheme is applied to the rate determining intramolecular proton transfer step in the enzyme human carbonic anhydrase II. The optimum reaction coordinate is determined with and without orthogonalization of the collective variables pertinent to a key conformational fluctuation and the actual proton transfer step at the active site of the enzyme. Suitability of the predicted reaction coordinates in different processes is examined in terms of the free energy profile projected along the reaction coordinate, the rate constant of transition and the underlying molecular mechanism of barrier crossing. Our results indicate that a better agreement with earlier simulation and experimental data is obtained when the orthogonalized collective variables are used to model the reaction coordinate.
Orthogonal order parameters are shown as ideal candidates for modeling of reaction coordinates for conformational fluctuation as well as intra-molecular proton transfer reactions in an enzyme using Classical and quantum mechanical-molecular mechanical (QM-MM) molecular dynamics interfaced with transition path sampling simulations. Display omitted
•How to choose important enzyme properties governing its turnover rate?•Mutually orthogonal parameters provide better models of reaction coordinate.•Successful prediction of free energy changes and rates of enzyme catalyzed reaction.
Bellamya bengalensis,
an edible mollusca, serves as a protein rich food source for the tribes in India. The objective of the present study was to isolate the protein fraction of the edible foot part ...of
B. bengalensis
for hydrolysis with three proteases, namely papain, pepsin, and alcalase.
B. bengalensis
protein isolates and hydrolysates were characterised for the functional properties like protein solubility index, emulsifying property, foaming property. The proximate composition of the protein isolate was determined along with nutritional value that included biological value, protein efficiency ratio, amino acid score, nutritional index, essential amino acid index. The molecular weight distribution of the protein isolate and the three hydrolysates were analyzed by SDS-PAGE. The hydrolysates were fractionated by ultrafiltration and the in vitro antioxidative properties were measured. The antihypertensive property of the in vitro angiotensin converting enzyme inhibitory activity of the hydrolysates was compared with the standard drug lisinopril. Thus, the results indicated that the hydrolyzed peptides had potent antioxidative and antihypertensive activity. The enzyme pepsin and papain produced partially hydrolyzed peptides suitable for use in the bakery industry while alcalase hydrolysis resulted in shorter peptides with the antihypertensive activity that may be used as a promising nutraceutical.
Graphic abstract
The mutant His-107-Tyr of human carbonic anhydrase II (HCA II) is highly unstable and has long been linked to a misfolding disease known as carbonic anhydrase deficiency syndrome (CADS). High ...temperature unfolding trajectories of the mutant are obtained from classical molecular dynamics simulations and analyzed in a multi-dimensional property space. When projected along a reaction coordinate these trajectories yield four distinguishable sets of structures that map qualitatively to folding intermediates of this mutant postulated earlier from experiments. We present in this article a detailed analysis of representative structures and proton transfer activity of these intermediates. It is also suggested that under suitable experimental conditions, these intermediates may be distinguished using circular dichroism (CD) spectroscopy.
Graphical Abstract.
We present a novel computational methodology of extracting representative structures of putative unfolding intermediates of a large protein from high temperature classical MD simulations. The extracted structures are investigated to assess their aggregation propensity and projected catalytic activity.
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