Showing papers in "Journal of Computational Chemistry in 2020"
TL;DR: An update on recently developed methodology and functionality in the computer program Local Orbital Basis Suite Toward Electronic‐Structure Reconstruction (LOBSTER), which has been improved by taking into account time‐reversal symmetry, thereby speeding up the DFT and LOBSTER calculations by a factor of 2.
Abstract: We present an update on recently developed methodology and functionality in the computer program Local Orbital Basis Suite Toward Electronic-Structure Reconstruction (LOBSTER) for chemical-bonding analysis in periodic systems. LOBSTER is based on an analytic projection from projector-augmented wave (PAW) density-functional theory (DFT) computations (Maintz et al., J. Comput. Chem. 2013, 34, 2557), reconstructing chemical information in terms of local, auxiliary atomic orbitals and thereby opening the output of PAW-based DFT codes to chemical interpretation. We demonstrate how LOBSTER has been improved by taking into account time-reversal symmetry, thereby speeding up the DFT and LOBSTER calculations by a factor of 2. Over the recent years, the functionalities have also been continually expanded, including accurate projected densities of states (DOSs), crystal orbital Hamilton population (COHP) analysis, atomic and orbital charges, gross populations, and the recently introduced k-dependent COHP. The software is offered free-of-charge for non-commercial research.
398 citations
TL;DR: Segmented all‐electron relativistically contracted (SARC) basis sets are presented for the elements 37Rb–54Xe, for use with the second‐order Douglas–Kroll–Hess approach and the zeroth‐order regular approximation.
Abstract: Segmented all-electron relativistically contracted (SARC) basis sets are presented for the elements 37 Rb-54 Xe, for use with the second-order Douglas-Kroll-Hess approach and the zeroth-order regular approximation. The basis sets have a common set of exponents produced with established heuristic procedures, but have contractions optimized individually for each scalar relativistic Hamiltonian. Their compact size and loose segmented contraction, which is in line with the construction of SARC basis sets for heavier elements, makes them suitable for routine calculations on large systems and when core spectroscopic properties are of interest. The basis sets are of triple-zeta quality and come in singly or doubly polarized versions, which are appropriate for both density functional theory and correlated wave function theory calculations. The quality of the basis sets is assessed against large decontracted reference basis sets for a number of atomic and ionic properties, while their general applicability is demonstrated with selected molecular examples.
76 citations
TL;DR: The present work aims to provide a comprehensive review of the performed numerical researches using Comsol Multiphysics to solve the physical governing equations of the heat transfer in advanced ceramics.
Abstract: Numerical simulation is a powerful tool to predict the physical behavior of the designed devices. This method provides detailed information about the investigated phenomenon at each point of the device which is sometimes impossible by experiments. Comsol Multiphysics is a powerful tool that can cover a wide range of engineering fields. This software has employed the finite element method (FEM) to solve the physical governing equations. Owing to the importance of the heat transfer in advanced ceramics, and the potential of the numerical methods in the solution of the related problems, the present work aims to provide a comprehensive review of the performed numerical researches using Comsol Multiphysics.
76 citations
TL;DR: The results at the DFT level using the B3LYP functional and the def2‐TZVP basis set show that the choice of the solute cavity does neither affect the accuracy nor the cost of calculations for small systems (< 100 atoms, and for larger systems, the use of a vdW‐type cavity is recommended, as it prevents small oscillations in the gradient which affect the convergence of the SCF energy gradient.
Abstract: The treatment of the solvation charges using Gaussian functions in the polarizable continuum model results in a smooth potential energy surface. These charges are placed on top of the surface of the solute cavity. In this article, we study the effect of the solute cavity (van der Waals-type or solvent-excluded surface-type) using the Gaussian charge scheme within the framework of the conductor-like polarizable continuum model on (a) the accuracy and computational cost of the self-consistent field (SCF) energy and its gradient and on (b) the calculation of free energies of solvation. For that purpose, we have considered a large set of systems ranging from few atoms to more than 200 atoms in different solvents. Our results at the DFT level using the B3LYP functional and the def2-TZVP basis set show that the choice of the solute cavity does neither affect the accuracy nor the cost of calculations for small systems (< 100 atoms). For larger systems, the use of a vdW-type cavity is recommended, as it prevents small oscillations in the gradient (present when using a SES-type cavity), which affect the convergence of the SCF energy gradient. Regarding the free energies of solvation, we consider a solvent-dependent probe sphere to construct the solvent-accessible surface area required to calculate the nonelectrostatic contribution to the free energy of solvation. For this part, our results for a large set of organic molecules in different solvents agree with available experimental data with an accuracy lower than 1 kcal/mol for both polar and nonpolar solvents.
64 citations
TL;DR: CNN’s architectures applying transfer learning and deep feature extraction are evaluated, and the result obtained shows that SVM is the best classifier for leaf's diseases detection.
Abstract: Nowadays, crop diseases are a crucial problem to the world’s food supplies, in a world where the population count is around 7 billion people, with more than 90% not getting access to the use of tools or features that would identify and solve the problem At present, we live in a world dominated by technology on a significant scale, major network coverage, high-end smart-phones, as long as there are great discoveries and improvements in AI The combination of high-end smart-phones and computer vision via Deep Learning has made possible what can be defined as “smartphone-assisted disease diagnosis” In the area of Deep Learning, multiple architecture models have been trained, some achieving performance reaching more than 9953% [1] In this study, we evaluate CNN’s architectures applying transfer learning and deep feature extraction All the features obtained will also be classified by SVM and KNN Our work is feasible by the use of the open source Plant Village Dataset The result obtained shows that SVM is the best classifier for leaf’s diseases detection
57 citations
TL;DR: In this paper, a review on the PVA/CMC composites for high potential of them on various properties (e.g. drug delivery, food packaging, agriculture, electric and physiochemical properties).
Abstract: Polyvinyl alcohol / Carboxiy methyl cellulose (PVA/CMC) composite based on the synergic relation between two polymer, which attract considerable and develop a new blend with enhanced properties. Moreover, PVA is a kind of versatile polymer and contains high mechanical applications. On the other hand, although CMC possesses effective application due to its high biocompatibility and biodegradability, it shows weak mechanical properties. Therefore, this paper provides a review on the PVA/CMC composites for high potential of them on various properties (e.g. drug delivery, food packaging, agriculture, electric and physiochemical properties). Finally, it was found that these novel composites can alternative source for producing biomaterials and drug delivery systems as well as hydrogel networks are constructed from these hydrophilic polymers for hydrophilic drugs or holding water to deliver moisture to the wound site. Moreover these composite can provide controlled release fertilizer as effective application in agriculture. Thus, PVA/CMC composites based materials have a wide applicability and nice potential in the development of physiochemical and electrical properties.
49 citations
TL;DR: The implementation and benchmarking of a Time Dependent Density Functional Theory approach in conjunction with Double Hybrid (DH) functionals show that these functionals provide results with an accuracy comparable to that of adjusted range‐separated functionals, with the relevant difference that for DHs no parameter is tuned on specific compounds thus making them more appealing for a general use.
Abstract: In this paper we present the implementation and benchmarking of a Time Dependent Density Functional Theory approach in conjunction with Double Hybrid (DH) functionals. We focused on the analysis of their performance for through space charge-transfer (CT) excitations which are well known to be very problematic for commonly used functionals, such as global hybrids.Two different families of functionals were compared, each of them containing pure, hybrid and double-hybrid functionals.The results obtained show that, beside the robustness of the implementation, these functionals provide results with an accuracy comparable to that of adjusted range-separated functionals, with the relevant difference that for DHs no parameter is tuned on specific compounds thus making them more appealing for a general use. Furthermore, the algorithm described and implemented is characterized by the same computational cost scaling as that of the ground state algorithm employed for MP2 and double hybrids.
43 citations
TL;DR: The study finds that even in favorable circumstances, TD‐DFT excited‐state geometries appear intrinsically and comparatively less accurate than DFT ground‐state ones.
Abstract: In this work, we take a different angle to the benchmarking of time-dependent density functional theory (TD-DFT) for the calculation of excited-state geometries by extensively assessing how accurate such geometries are compared to ground-state geometries calculated with ordinary DFT. To this end, we consider 20 medium-sized aromatic organic compounds whose lowest singlet excited states are ideally suited for TD-DFT modeling and are very well described by the approximate coupled-cluster singles and doubles (CC2) method, and then use this method and six different density functionals (BP86, B3LYP, PBE0, M06-2X, CAM-B3LYP, and ωB97XD) to optimize the corresponding ground- and excited-state geometries. The results show that although each hybrid functional reproduces the CC2 excited-state bond lengths very satisfactorily, achieving an overall root mean square error of 0.011 A for all 336 bonds in the 20 molecules, these errors are distinctly larger than those of only 0.004-0.006 A with which the hybrid functionals reproduce the CC2 ground-state bond lengths. Furthermore, for each functional employed, the variation in the error relative to CC2 between different molecules is found to be much larger (by at least a factor of 3) for the excited-state geometries than for the ground-state geometries, despite the fact that the molecules/states under investigation have rather uniform chemical and spectroscopic character. Overall, the study finds that even in favorable circumstances, TD-DFT excited-state geometries appear intrinsically and comparatively less accurate than DFT ground-state ones.
43 citations
TL;DR: Several of the B97(M)‐based methods—particularly the DFT‐D4 versions—surpass the accuracy of previously studied methods for peptide conformer, water hexamer, and transition‐metal complex geometries, making them safe‐to‐use, cost‐efficient alternatives to the original methods.
Abstract: Previously, we introduced DFT-D3(BJ)ωB97X-V and ωB97M-V functionals and assessed them for the GMTKN55 database [Najibi and Goerigk, J Chem. Theory Comput. 2018, 14, 5725]. In this study, we present DFT-D4 damping parameters to build the DFT-D4 counterparts of these functionals and assess these in comparison. We extend our analysis beyond GMTKN55 and especially turn our attention to enzymatically catalyzed and metal-organic reactions. We find that B97M-D4 is now the second-best performing meta-generalized-gradient approximation functional for the GMTKN55 database and it can provide noticeably better organometallic reaction energies compared to B97M-D3(BJ). Moreover, the aforementioned DFT-D3(BJ)-based functionals have not been thoroughly assessed for geometries and herein we close this gap by analyzing geometries of noncovalently bound dimers and trimers, peptide conformers, water hexamers and transition-metal complexes. We find that several of the B97(M)-based methods-particularly the DFT-D4 versions-surpass the accuracy of previously studied methods for peptide conformer, water hexamer, and transition-metal complex geometries, making them safe-to-use, cost-efficient alternatives to the original methods. The DFT-D4 variants can be easily used with ORCA4.1 and above.
42 citations
TL;DR: Atomistic simulation provides framework for enhanced fitness and higher transmissibility in D614G SARS‐COV‐2 mutant by delineating a plausible mechanism and providing evidence that D614g sgp mutant is more available for receptor binding, cellular invasion and reduced antibody interaction.
Abstract: D614G spike glycoprotein (sgp) mutation in rapidly spreading severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) is associated with enhanced fitness and higher transmissibility in new cases of COVID-19 but the underlying mechanism is unknown. Here, using atomistic simulation, a plausible mechanism has been delineated. In G614 sgp but not wild type, increased D(G)614-T859 Cα-distance within 65 ns is interpreted as S1/S2 protomer dissociation. Overall, ACE2-binding, post-fusion core, open-state and sub-optimal antibody-binding conformations were preferentially sampled by the G614 mutant, but not wild type. Furthermore, in the wild type, only one of the three sgp chains has optimal communication route between residue 614 and the receptor-binding domain (RBD); whereas, two of the three chains communicated directly in G614 mutant. These data provide evidence that D614G sgp mutant is more available for receptor binding, cellular invasion and reduced antibody interaction; thus, providing framework for enhanced fitness and higher transmissibility in D614G SARS-COV-2 mutant.
41 citations
TL;DR: The FFParam package has been designed to facilitate the parametrization process and provides all the features required for generation and analysis of CHARMM and Drude FF parameters for small molecules.
Abstract: Accurate force-field (FF) parameters are key to reliable prediction of properties obtained from molecular modeling (MM) and molecular dynamics (MD) simulations. With ever-widening applicability of MD simulations, robust parameters need to be generated for a wider range of chemical species. The CHARMM General Force Field program (CGenFF, https://cgenff.umaryland.edu/) is a tool for obtaining initial parameters for a given small molecule based on analogy with the available CGenFF parameters. However, improvement of these parameters is often required and performing their optimization remains tedious and time consuming. In addition, tools for optimization of small molecule parameters in the context of the Drude polarizable FF are not yet available. To overcome these issues, the FFParam package has been designed to facilitate the parametrization process. The package includes a graphical user interface (GUI) created using Qt libraries. FFParam supports Gaussian and Psi4 for performing quantum mechanical calculations and CHARMM and OpenMM for MM calculations. A Monte Carlo simulated annealing (MCSA) algorithm has been implemented for automated fitting of partial atomic charge, atomic polarizabilities and Thole scale parameters. The LSFITPAR program is called for automated fitting of bonded parameters. Accordingly, FFParam provides all the features required for generation and analysis of CHARMM and Drude FF parameters for small molecules. FFParam-GUI includes a text editor, graph plotter, molecular visualization, and text to table converter to meet various requirements of the parametrization process. It is anticipated that FFParam will facilitate wider use of CGenFF as well as promote future use of the Drude polarizable FF.
TL;DR: In this article, an algorithm for rolling and automated micro-solvation of solutes is presented, which takes conformational sampling and rearrangements in the solvent shell into account.
Abstract: Solvation is a notoriously difficult and nagging problem for the rigorous theoretical description of chemistry in the liquid phase. Successes and failures of various approaches ranging from implicit solvation modeling through dielectric continuum embedding and microsolvated quantum chemical modeling to explicit molecular dynamics highlight this situation. Here, we focus on quantum chemical microsolvation and discuss an explicit conformational sampling ansatz to make this approach systematic. For this purpose, we introduce an algorithm for rolling and automated microsolvation of solutes. Our protocol takes conformational sampling and rearrangements in the solvent shell into account. Its reliability is assessed by monitoring the evolution of the spread and average of the observables of interest.
TL;DR: In this article, a review of surface modification of zirconia incorporating hydroxyapatite (HAp) is presented, where the advantages, disadvantages, biocompatibility, strength, and osseointergration and biointegration properties of the presented composites are explored.
Abstract: Zirconia has garnered significant attention as a new ceramic material for dental implant due to its excellent biocompatibility, strength, and promoting the oral rehabilitation with high aesthetic, biological and mechanical properties. It also expedites the amelioration of bone minerals surface by its bio-integrative ingredients which are naturally close to ceramic intrinsic of bone. Alternatively, hydroxyapatite (HAp) has prevalently been used in dental implant due to its high biocompatibility. However, it generally shows weak strength and mechanical properties. Consequently, incorporating zirconia and HAp produces appropriate composites for dental implant having improved physiochemical properties. This review provides discussions addressing the methodologies and exemplars for the designed composites used in dental implant applications. The representative methods for surface modification of zirconia incorporating HAp (i.e. sol-gel, hot isostatic pressing, plasma spraying, electrophoretic deposition, etc.) is highlighted. The advantages, disadvantages, biocompatibility, strength, and osseointergration and biointegration properties of the presented composites are explored.
TL;DR: It is found that the protein matrix in P450 OleTJE acts as a moderate catalyst and that orienting an external electric field along the Fe─O bond of compound I has the biggest impact on the reaction barrier.
Abstract: We present here a versatile computational code named "elecTric fIeld generaTion And maNipulation (TITAN)," capable of generating various types of external electric fields, as well as quantifying the local (or intrinsic) electric fields present in proteins and other biological systems according to Coulomb's Law. The generated electric fields can be coupled with quantum mechanics (QM), molecular mechanics (MM), QM/MM, and molecular dynamics calculations in most available software packages. The capabilities of the TITAN code are illustrated throughout the text with the help of examples. We end by presenting an application, in which the effects of the local electric field on the hydrogen transfer reaction in cytochrome P450 OleTJE enzyme and the modifications induced by the application of an oriented external electric field are examined. We find that the protein matrix in P450 OleTJE acts as a moderate catalyst and that orienting an external electric field along the Fe─O bond of compound I has the biggest impact on the reaction barrier. The induced catalysis/inhibition correlates with the calculated spin density on the O-atom. © 2019 Wiley Periodicals, Inc.
TL;DR: In this paper, the effect of processing methods on carbon nanotube distribution and enhancement of mechanical properties such as toughness, wear behavior and hardness of the nanocomposites are reviewed.
Abstract: Carbon nanotubes (CNTs)-reinforced aluminum composites have attracted attention due to their high specific strength low density, which makes them suitable for the use in aerospace and automobile industries. In this review, preparation methods of Al/CNTs composites for achieving a homogeneous desperation of the CNT in the Al matrix are summarized. In addition, the effect of processing methods on carbon nanotube distribution and enhancement of mechanical properties such as toughness, wear behavior and hardness of the nanocomposites are reviewed. Improvement of mechanical characteristics was observed by the incorporation of carbon nanotubes in aluminum matrix. The strengthening factors gained by the carbon nanotubes addition are the interface of metal and CNTs and the chemical and structural stability of CNTs.
TL;DR: During REP simulations, the system can easily escape from being trapped in local minima by exchanging configurations with high temperatures, resulting in significant improvement in the accuracy and precision of protein–ligand binding affinity calculations.
Abstract: Determination of the ligand-binding affinity is an extremely interesting problem. Normally, the free energy perturbation (FEP) method provides an appropriate result. However, it is of great interest to improve the accuracy and precision of this method. In this context, temperature replica exchange molecular dynamics implementation of the FEP computational approach, which we call replica exchange free energy perturbation (REP) was proposed. In particular, during REP simulations, the system can easily escape from being trapped in local minima by exchanging configurations with high temperatures, resulting in significant improvement in the accuracy and precision of protein-ligand binding affinity calculations. The distribution of the decoupling free energy was enlarged, and its mean values were decreased. This results in changes in the magnitude of the calculated binding free energies as well as in alteration in the binding mechanism. Moreover, the REP correlation coefficient with respect to experiment ( RREP = 0.85 ± 0.15) is significantly boosted in comparison with the FEP one ( RFEP = 0.64 ± 0.30). Furthermore, the root-mean-square error (RMSE) of REP is also smaller than FEP, RMSEREP = 4.28 ± 0.69 versus RMSEFEP = 5.80 ± 1.11 kcal/mol, respectively. © 2019 Wiley Periodicals, Inc.
TL;DR: Several semiempirical and density‐functional theory methods are assessed for their ability to describe the potential energy surface and reaction energies of the covalent modification of a thiol by an electrophile.
Abstract: Targeted covalent inhibitor drugs require computational methods that go beyond simple molecular-mechanical force fields in order to model the chemical reactions that occur when they bind to their targets. Here, several semiempirical and density-functional theory (DFT) methods are assessed for their ability to describe the potential energy surface and reaction energies of the covalent modification of a thiol by an electrophile. Functionals such as PBE and B3LYP fail to predict a stable enolate intermediate. This is largely due to delocalization error, which spuriously stabilizes the prereaction complex, in which excess electron density is transferred from the thiolate to the electrophile. Functionals with a high-exact exchange component, range-separated DFT functionals, and variationally optimized exact exchange (i.e., the LC-B05minV functional) correct this issue to various degrees. The large gradient behavior of the exchange enhancement factor is also found to significantly affect the results, leading to the improved performance of PBE0. While ωB97X-D and M06-2X were reasonably accurate, no method provided quantitative accuracy for all three electrophiles, making this a very strenuous test of functional performance. Additionally, one drawback of M06-2X was that molecular dynamics (MD) simulations using this functional were only stable if a fine integration grid was used. The low-cost semiempirical methods, PM3, AM1, and PM7, provide a qualitatively correct description of the reaction mechanism, although the energetics is not quantitatively reliable. As a proof of concept, the potential of mean force for the addition of methylthiolate to methylvinyl ketone was calculated using quantum mechanical/molecular mechanical MD in an explicit polarizable aqueous solvent. © 2019 Wiley Periodicals, Inc.
TL;DR: PSIXAS, a recent implementation for simulating NEXAFS and PP‐NexAFS spectra by means of the transition‐potential and the Δ‐Kohn–Sham method, is presented and found that larger, extended basis sets are needed to obtain more accurate absolute resonance positions.
Abstract: Near edge X-ray absorption fine structure (NEXAFS) spectra and their pump-probe extension (PP-NEXAFS) offer insights into valence- and core-excited states. We present PSIXAS, a recent implementation for simulating NEXAFS and PP-NEXAFS spectra by means of the transition-potential and the Δ-Kohn-Sham method. The approach is implemented in form of a software plugin for the Psi4 code, which provides access to a wide selection of basis sets as well as density functionals. We briefly outline the theoretical foundation and the key aspects of the plugin. Then, we use the plugin to simulate PP-NEXAFS spectra of thymine, a system already investigated by others and us. It is found that larger, extended basis sets are needed to obtain more accurate absolute resonance positions. We further demonstrate that, in contrast to ordinary NEXAFS simulations, where the choice of the density functional plays a minor role for the shape of the spectrum, for PP-NEXAFS simulations the choice of the density functional is important. Especially hybrid functionals (which could not be used straightforwardly before to simulate PP-NEXAFS spectra) and their amount of "Hartree-Fock like" exact exchange affects relative resonance positions in the spectrum.
TL;DR: In this paper, a review of bioactive glass coatings on zirconia as well as surface modification methods (i.e., sol-gel, laser cladding, plasma spraying, etc.) is provided.
Abstract: Nowadays zirconia, due to its interesting properties e.g. biocompatibility, strength, aesthetic, chemical and mechanical properties, has got lots of attention for dental implants. On the other hand, bioactive glasses have been used as coating on tougher substrates such as zirconia. Bioactive glass coatings can decrease the healing time and hence accelerate the formation of the bond between bone and implant. Hence in this study, we introduce the novel zirconia/bioactive glass composites with high mechanical strength and bioactivity to achieve the ideal implant dentistry. Furthermore, a review of bioactive glass coatings (i.e. 45S5 and 58S) on zirconia as well as surface modification methods (i.e. sol-gel, laser cladding, plasma spraying, etc.) is provided.
TL;DR: Evaluated deformations of different shape, amplitude, and range demonstrates that the macroscopic bending modulus assumed by the Helfrich–Canham model is increasingly unsuitable below the 100‐Å scale, and direct free‐energy calculations reveal a much greater plasticity.
Abstract: We report a methodology to calculate the free energy of a shape transformation in a lipid membrane directly from a molecular dynamics simulation. The bilayer need not be homogeneous or symmetric and can be atomically detailed or coarse grained. The method is based on a collective variable that quantifies the similarity between the membrane and a set of predefined density distributions. Enhanced sampling of this "Multi-Map" variable re-shapes the bilayer and permits the derivation of the corresponding potential of mean force. Calculated energies thus reflect the dynamic interplay of atoms and molecules, rather than postulated effects. Evaluation of deformations of different shape, amplitude, and range demonstrates that the macroscopic bending modulus assumed by the Helfrich-Canham model is increasingly unsuitable below the 100-A scale. In this range of major biological significance, direct free-energy calculations reveal a much greater plasticity. We also quantify the stiffening effect of cholesterol on bilayers of different composition and compare with experiments. Lastly, we illustrate how this approach facilitates analysis of other solvent reorganization processes, such as hydrophobic hydration. Published 2019. This article is a U.S. Government work and is in the public domain in the USA.
TL;DR: GaMD enhanced simulations have revealed strongly coupled dynamics of the GPCR and lipids that depend on the receptor activation state and identified important regions of the receptor that interacted distinctly with the lipids in highly correlated manner.
Abstract: G-protein-coupled receptors (GPCRs) are the largest family of human membrane proteins and serve as primary targets of approximately one-third of currently marketed drugs. In particular, adenosine A1 receptor (A1 AR) is an important therapeutic target for treating cardiac ischemia-reperfusion injuries, neuropathic pain, and renal diseases. As a prototypical GPCR, the A1 AR is located within a phospholipid membrane bilayer and transmits cellular signals by changing between different conformational states. It is important to elucidate the lipid-protein interactions in order to understand the functional mechanism of GPCRs. Here, all-atom simulations using a robust Gaussian accelerated molecular dynamics (GaMD) method were performed on both the inactive (antagonist bound) and active (agonist and G-protein bound) A1 AR, which was embedded in a 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) lipid bilayer. In the GaMD simulations, the membrane lipids played a key role in stabilizing different conformational states of the A1 AR. Our simulations further identified important regions of the receptor that interacted distinctly with the lipids in highly correlated manner. Activation of the A1 AR led to differential dynamics in the upper and lower leaflets of the lipid bilayer. In summary, GaMD enhanced simulations have revealed strongly coupled dynamics of the GPCR and lipids that depend on the receptor activation state. © 2019 Wiley Periodicals, Inc.
TL;DR: It is demonstrated that concurrent binding of multiple anionic lipids by GRP1‐PHD contributes to its membrane affinity, which in turn control its signaling activity.
Abstract: The pleckstrin homology (PH) domain of general receptor for phosphoionositides 1 (GRP1-PHD) binds specifically to phosphatidylinositol (3,4,5)-triphosphate (PIP3 ), and acts as a second messenger. Using an extensive array of molecular dynamics (MD) simulations employing highly mobile membrane mimetic (HMMM) model as well as complementary full membrane simulations, we capture differentiable binding and dynamics of GRP1-PHD in the presence of membranes containing PC, PS, and PIP3 lipids in varying compositions. While GRP1-PHD forms only transient interactions with pure PC membranes, incorporation of anionic lipids resulted in stable membrane-bound configurations. We report the first observation of two distinct PIP3 binding modes on GRP1-PHD, involving PIP3 interactions at a "canonical" and at an "alternate" site, suggesting the possibility of simultaneous binding of multiple anionic lipids. The full membrane simulations confirmed the stability of the membrane bound pose of GRP1-PHD as captured from our HMMM membrane binding simulations. By performing additional steered membrane unbinding simulations and calculating nonequilibrium work associated with the process, as well as metadynamics simulations, on the protein bound to full membranes, allowing for more quantitative examination of the binding strength of the GRP1-PHD to the membrane, we demonstrate that along with the bound PIP3 , surrounding anionic PS lipids increase the energetic cost of unbinding of GRP1-PHD from the canonical mode, causing them to dissociate more slowly than the alternate mode. Our results demonstrate that concurrent binding of multiple anionic lipids by GRP1-PHD contributes to its membrane affinity, which in turn control its signaling activity. © 2019 Wiley Periodicals, Inc.
TL;DR: The optimized Drude‐2013 protein polarizable FF leads to a significant improvement in reproducing the ion‐π pair distances observed in experimental protein structures, as well as a smaller root‐mean‐square differences and fluctuations of the overall protein structures from experimental structures.
Abstract: Cation-π interactions are noncovalent interactions between a π-electron system and a positively charged ion that are regarded as a strong noncovalent interaction and are ubiquitous in biological systems. Similarly, though less studied, anion-ring interactions are present in proteins along with in-plane interactions of anions with aromatic rings. As these interactions are between a polarizing ion and a polarizable π system, the accuracy of the treatment of these interactions in molecular dynamics (MD) simulations using additive force fields (FFs) may be limited. In the present work, to allow for a better description of ion-π interactions in proteins in the Drude-2013 protein polarizable FF, we systematically optimized the parameters for these interactions targeting model compound quantum mechanical (QM) interaction energies with atom pair-specific Lennard-Jones parameters along with virtual particles as selected ring centroids introduced to target the QM interaction energies and geometries. Subsequently, MD simulations were performed on a series of protein structures where ion-π pairs occur to evaluate the optimized parameters in the context of the Drude-2013 FF. The resulting FF leads to a significant improvement in reproducing the ion-π pair distances observed in experimental protein structures, as well as a smaller root-mean-square differences and fluctuations of the overall protein structures from experimental structures. Accordingly, the optimized Drude-2013 protein polarizable FF is suggested for use in MD simulations of proteins where cation-π and anion-ring interactions are critical. © 2019 Wiley Periodicals, Inc.
TL;DR: In this paper, an extensive investigation in the field of optical applications of nanocomposite materials has been conducted, where an optically functional phase is embedded in a transparent, processable matrix.
Abstract: There has been an extensive investigation in the field of optical applications of nanocomposite materials. To prepare photosensitive nanocomposites, an optically functional phase is embedded in a transparent, processable matrix. This provides the opportunity to utilize the optical properties in other forms including fibers and films, which are more technologically important. Due to expansion of optical materials applications, novel transparent materials and optically functional are required. Recent optical nanocomposites and their applications in different areas especially catalysis and drug delivery have been addressed in this paper.
TL;DR: It was found that the PBE + U method yields a strongly distorted monoclinic phase and does not reproduce the metal‐to‐insulator transition of VO2 correctly, even with modified values of Ueff, while the functional SCAN yields the optimal balance between computational efficiency and accuracy.
Abstract: In a previous study (Stahl and Bredow, Chem. Phys. Lett. 2018, 695, 28-33), we have studied structural, energetic, and electronic properties of two vanadium dioxide VO2 polymorphs with modified global and range-separated hybrid functionals. Since hybrid methods are computationally demanding, we evaluate the computationally more efficient DFT + U method in the present study. We assessed the widely used Dudarev PBE + U approach with a literature value of the effective Hubbard parameter Ueff = 3.4 eV. We compared the PBE + U results for the two VO2 polymorphs with our previous results, a self-consistent hybrid functional sc-PBE0, and the meta-GGA functional SCAN. It was found that the PBE + U method yields a strongly distorted monoclinic phase and does not reproduce the metal-to-insulator transition of VO2 correctly, even with modified values of Ueff . On the other hand, sc-PBE0 and SCAN describe the relative stability and the electronic structure of both polymorphs correctly and also provide reasonable lattice parameters. The functional SCAN yields the optimal balance between computational efficiency and accuracy. © 2019 The Authors. Journal of Computational Chemistry published by Wiley Periodicals, Inc.
TL;DR: A replica‐exchange based scheme employing different levels of a repulsive biasing between partners in each replica simulation without affecting interactions within each protein or with the solvent.
Abstract: The realistic prediction of protein-protein complex structures is import to ultimately model the interaction of all proteins in a cell and for the design of new protein-protein interactions. In principle, molecular dynamics (MD) simulations allow one to follow the association process under realistic conditions including full partner flexibility and surrounding solvent. However, due to the many local binding energy minima at the surface of protein partners, MD simulations are frequently trapped for long times in transient association states. We have designed a replica-exchange based scheme employing different levels of a repulsive biasing between partners in each replica simulation. The bias acts only on intermolecular interactions based on an increase in effective pairwise van der Waals radii (repulsive scaling (RS)-REMD) without affecting interactions within each protein or with the solvent. For a set of five protein test cases (out of six) the RS-REMD technique allowed the sampling of near-native complex structures even when starting from the opposide site with respect to the native binding site for one partner. Using the same start structures and same computational demand regular MD simulations sampled near native complex structures only for one case. The method showed also improved results for the refinement of docked structures in the vicinity of the native binding geometry compared to regular MD refinement.
TL;DR: This work proposes in this work a direct approach to compute the solvation energies of the proton in ammonia from large‐sized neutral and protonated ammonia clusters, and calculates the absolute solvation free energy and theabsolute solvation enthalpy.
Abstract: The absolute solvation energies (free energies and enthalpies) of the proton in ammonia are used to compute the pKa of species embedded in ammonia. They are also used to compute the solvation energies of other ions in ammonia. Despite their importance, it is not possible to determine experimentally the solvation energies of the proton in a given solvent. We propose in this work a direct approach to compute the solvation energies of the proton in ammonia from large-sized neutral and protonated ammonia clusters. To undertake this investigation, we performed a geometry optimization of neutral and protonated ammonia 30-mer, 40-mer, and 50 mer to locate stable structures. These structures have been fully optimized at both APFD/6-31++g(d,p) and M06-2X/6-31++g(d,p) levels of theory. An infrared spectroscopic study of these structures has been provided to assess the reliability of our investigation. Using these structures, we have computed the absolute solvation free energy and the absolute solvation enthalpy of the proton in ammonia. It comes out that the absolute solvation free energy of the proton in ammonia is calculated to be -1192 kJ mol-1 , whereas the absolute solvation enthalpy is evaluated to be -1214 kJ mol-1 . © 2019 Wiley Periodicals, Inc.
TL;DR: This work discusses the results of three previously published studies of ligand binding and presents results where the correction scheme was used to correct independent free energies obtained from simulations employing a cutoff scheme or LS electrostatics.
Abstract: Alchemically derived free energies are artifacted when the perturbed moiety has a nonzero net charge. The source of the artifacts lies in the effective treatment of the electrostatic interactions within and between the perturbed atoms and remaining (partial) charges in the simulated system. To treat the electrostatic interactions effectively, lattice-summation (LS) methods or cutoff schemes in combination with a reaction-field contribution are usually employed. Both methods render the charging component of the calculated free energies sensitive to essential parameters of the system like the cutoff radius or the box side lengths. Here, we discuss the results of three previously published studies of ligand binding. These studies presented estimates of binding free energies that were artifacted due to the charged nature of the ligands. We show that the size of the artifacts can be efficiently calculated and raw simulation data can be corrected. We compare the corrected results with experimental estimates and nonartifacted estimates from path-sampling methods. Although the employed correction scheme involves computationally demanding continuum-electrostatics calculations, we show that the correction estimate can be deduced from a small sample of configurations rather than from the entire ensemble. This observation makes the calculations of correction terms feasible for complex biological systems. To show the general applicability of the proposed procedure, we also present results where the correction scheme was used to correct independent free energies obtained from simulations employing a cutoff scheme or LS electrostatics. In this work, we give practical guidelines on how to apply the appropriate corrections easily.
TL;DR: This review has focused on the mechanisms and properties of SMAs and SMPs as promising materials for stent application.
Abstract: Stents are nets which open a stenotic vessel, therefore allowing restoration of the blood stream to peripheral tissues. The advantage of the self-expandable stent with respect to the stainless steel one is that it does not need balloon expansion which possess the risks of further damage of the vascular tissue due to its inflation, it does not require an overexpansion to account for the elastic recoil, and, when positioned, it exerts on the artery a constant force (due to the plateau) unless the artery does not try to occlude the device. The disadvantage, in case of calcified plaques, is that the stent is not able to bring the vessel lumen to the original healthy dimensions. Self-expandable stents are used to treat atherosclerotic lesions in the coronary arteries, the carotid arteries, and in the peripheral arteries. Shape memory alloys, mainly NiTi, are used in numerous applications of the self-expandable vascular stents. Ni-Ti is widely implemented for implants and medical devices because of its excellent biocompatibility, mechanical characteristics, and fatigue performance that make it particularly indicated for long-term installations. Another material for cardiovascular stents are shape memory polymers (SMPs). They provide protection of small blood vessels from collapse, thanks to SME triggered by temperature change or polymer’s hydration. This review has focused on the mechanisms and properties of SMAs and SMPs as promising materials for stent application.
TL;DR: The virtual‐reality framework AVATAR (Advanced Virtual Approach to Topological Analysis of Reactivity) for the immersive exploration of potential‐energy landscapes is presented and examples including the discovery of competitive reaction paths in simple A + BC collisional systems and the interconversion between conformers in ring‐puckering motions of flexible rings highlight the innovation potential that augmented and virtual reality convey for teaching, training, and supporting research in chemistry.
Abstract: The virtual-reality framework AVATAR (Advanced Virtual Approach to Topological Analysis of Reactivity) for the immersive exploration of potential-energy landscapes is presented. AVATAR is based on modern consumer-grade virtual-reality technology and builds on two key concepts: (a) the reduction of the dimensionality of the potential-energy surface to two process-tailored, physically meaningful generalized coordinates, and (b) the analogy between the evolution of a chemical process and a pathway through valleys (potential wells) and mountain passes (saddle points) of the associated potential energy landscape. Examples including the discovery of competitive reaction paths in simple A + BC collisional systems and the interconversion between conformers in ring-puckering motions of flexible rings highlight the innovation potential that augmented and virtual reality convey for teaching, training, and supporting research in chemistry.