scholarly journals Accurate Receptor-Ligand Binding Free Energies from Fast QM Conformational Chemical Space Sampling

2021 ◽  
Vol 22 (6) ◽  
pp. 3078
Author(s):  
Esra Boz ◽  
Matthias Stein
Keyword(s):  
Density Functional ◽  
Chemical Space ◽  
Tight Binding ◽  
Free Ligand ◽  
Density Functional Theory Calculations ◽  
Conformational Space ◽  
Free Energies ◽  
Receptor Complexes ◽  
Experimental Values ◽  
Good Agreement

Small molecule receptor-binding is dominated by weak, non-covalent interactions such as van-der-Waals hydrogen bonding or electrostatics. Calculating these non-covalent ligand-receptor interactions is a challenge to computational means in terms of accuracy and efficacy since the ligand may bind in a number of thermally accessible conformations. The conformational rotamer ensemble sampling tool (CREST) uses an iterative scheme to efficiently sample the conformational space and calculates energies using the semi-empirical ‘Geometry, Frequency, Noncovalent, eXtended Tight Binding’ (GFN2-xTB) method. This combined approach is applied to blind predictions of the modes and free energies of binding for a set of 10 drug molecule ligands to the cucurbit[n]urils CB[8] receptor from the recent ‘Statistical Assessment of the Modeling of Proteins and Ligands’ (SAMPL) challenge including morphine, hydromorphine, cocaine, fentanyl, and ketamine. For each system, the conformational space was sufficiently sampled for the free ligand and the ligand-receptor complexes using the quantum chemical Hamiltonian. A multitude of structures makes up the final conformer-rotamer ensemble, for which then free energies of binding are calculated. For those large and complex molecules, the results are in good agreement with experimental values with a mean error of 3 kcal/mol. The GFN2-xTB energies of binding are validated by advanced density functional theory calculations and found to be in good agreement. The efficacy of the automated QM sampling workflow allows the extension towards other complex molecular interaction scenarios.

Towards a Design of Active Oxygen Evolution Catalysts: Insights from Automated Density Functional Theory Calculations and Machine Learning

2019 ◽  
Author(s):  
Seoin Back ◽  
Kevin Tran ◽  
Zachary Ulissi
Keyword(s):  
Machine Learning ◽  
Oxygen Evolution ◽  
Active Sites ◽  
Density Functional ◽  
Chemical Space ◽  
Density Functional Theory Calculations ◽  
Catalyst Design ◽  
Transition Metal Catalysts ◽  
Oxide Materials ◽  
Design Strategies

<div> <div> <div> <div><p>Developing active and stable oxygen evolution catalysts is a key to enabling various future energy technologies and the state-of-the-art catalyst is Ir-containing oxide materials. Understanding oxygen chemistry on oxide materials is significantly more complicated than studying transition metal catalysts for two reasons: the most stable surface coverage under reaction conditions is extremely important but difficult to understand without many detailed calculations, and there are many possible active sites and configurations on O* or OH* covered surfaces. We have developed an automated and high-throughput approach to solve this problem and predict OER overpotentials for arbitrary oxide surfaces. We demonstrate this for a number of previously-unstudied IrO2 and IrO3 polymorphs and their facets. We discovered that low index surfaces of IrO2 other than rutile (110) are more active than the most stable rutile (110), and we identified promising active sites of IrO2 and IrO3 that outperform rutile (110) by 0.2 V in theoretical overpotential. Based on findings from DFT calculations, we pro- vide catalyst design strategies to improve catalytic activity of Ir based catalysts and demonstrate a machine learning model capable of predicting surface coverages and site activity. This work highlights the importance of investigating unexplored chemical space to design promising catalysts.<br></p></div></div></div></div><div><div><div> </div> </div> </div>

scholarly journals Computational Study of Methane C–H Activation by Main Group and Mixed Main Group–Transition Metal Complexes

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2794
Author(s):  
Carly C. Carter ◽  
Thomas R. Cundari
Keyword(s):  
Transition Metal Complexes ◽  
Active Site ◽  
Density Functional ◽  
Computational Study ◽  
Divalent Metal ◽  
Main Group ◽  
Free Energies ◽  
Functional Theory ◽  
Activation Barriers ◽  
Experimental Values

In the present density functional theory (DFT) research, nine different molecules, each with different combinations of A (triel) and E (divalent metal) elements, were reacted to effect methane C–H activation. The compounds modeled herein incorporated the triels A = B, Al, or Ga and the divalent metals E = Be, Mg, or Zn. The results show that changes in the divalent metal have a much bigger impact on the thermodynamics and methane activation barriers than changes in the triels. The activating molecules that contained beryllium were most likely to have the potential for activating methane, as their free energies of reaction and free energy barriers were close to reasonable experimental values (i.e., ΔG close to thermoneutral, ΔG‡ ~30 kcal/mol). In contrast, the molecules that contained larger elements such as Zn and Ga had much higher ΔG‡. The addition of various substituents to the A–E complexes did not seem to affect thermodynamics but had some effect on the kinetics when substituted closer to the active site.

Graphene-Based Sensors for Monitoring Strain

2013 ◽  
Vol 3 (1) ◽  
pp. 74-83
Author(s):  
M. Mirnezhad ◽  
R. Ansari ◽  
H. Rouhi ◽  
M. Faghihnasiri
Keyword(s):  
Fermi Level ◽  
Band Gap ◽  
Strain Distribution ◽  
Density Functional ◽  
Tight Binding ◽  
Density Functional Theory Calculations ◽  
Generalized Gradient ◽  
Functional Theory ◽  
The Density Functional Theory ◽  
Gap Opening

The application of graphene as a nanosensor in measuring strain through its band structure around the Fermi level is investigated in this paper. The mechanical properties of graphene as well as its electronic structure are determined by using the density functional theory calculations within the framework of generalized gradient approximation. In the case of electronic properties, the simulations are applied for symmetrical and asymmetrical strain distributions in elastic range; also the tight-binding approach is implemented to verify the results. It is indicated that the energy band gap does not change with the symmetrical strain distribution but depend on the asymmetric strain distribution, increasing strain leads to band gap opening around the Fermi level.

scholarly journals Analysis of vibratinal spectra of 8-hydroxyquinoline and its 5,7-dichloro, 5,7-dibromo, 5,7-diiodo and 5,7-dinitro derivatives based on density functional theory calculations

2007 ◽  
Vol 5 (1) ◽  
pp. 201-220 ◽  
Author(s):  
Khaled Bahgat ◽  
Abdel Ragheb
Keyword(s):  
Density Functional Theory ◽  
Dft Calculations ◽  
Density Functional ◽  
Density Functional Theory Calculations ◽  
Basis Set ◽  
Normal Coordinate ◽  
Functional Theory ◽  
The Density Functional Theory ◽  
Vibrational Bands ◽  
Good Agreement

AbstractThe geometry, frequency and intensity of the vibrational bands of 8-hydroxyquinoline and its 5,7-dichloro, 5,7-dibromo, 5,7-diiodo and 5,7-dinitro derivatives were obtained by the density functional theory (DFT) calculations with Becke3-Lee-Parr (B3LYP) functional and 6-31G* basis set. The effects of chloride, bromide, iodide and nitro substituent on the vibrational frequencies of 8-hydroxyquinoline have been investigated. The assignments have been proposed with aid of the results of normal coordinate analysis. The observed and calculated spectra are found to be in good agreement.

scholarly journals Building Machine Learning Force Fields of Proteins with Fragment-Based Approach and Transfer Learning

2021 ◽  
Author(s):  
Zheng Cheng ◽  
Jiahui Du ◽  
Lei Zhang ◽  
Jing Ma ◽  
Wei Li ◽  
...  
Keyword(s):  
Machine Learning ◽  
Density Functional ◽  
Force Fields ◽  
Density Functional Theory Calculations ◽  
Md Simulations ◽  
Target System ◽  
Functional Theory ◽  
Protein Functions ◽  
Data Library ◽  
Good Agreement

<p>Molecular dynamic (MD) simulation plays an essential role in understanding protein functions at atomic level. At present, MD simulations on proteins are mainly based on classical force fields. However, the accuracy of classical force fields for proteins is still insufficient for accurate descriptions of their structures and dynamical properties. Here we present a novel protocol to construct machine learning force field (MLFF) for a given protein with full quantum mechanics (QM) accuracy. In this protocol, the energy of the target system is obtained by fitting energies of its various subsystems constructed with the generalized energy-based fragmentation (GEBF) approach. To facilitate the construction of MLFF for various proteins, a protein’s data library is created to store all data of subsystems generated from trained proteins. With this protein’s data library, for a new protein only its subsystems with new topological types are required for the construction of the corresponding MLFF. This protocol is illustrated with two polypeptides, 4ZNN and 1XQ8 segment, as examples. The energies and forces predicted from this MLFF are in good agreement with those from density functional theory calculations, and dihedral angle distributions from GEBF-MLFF MD simulations can also well reproduce those from <i>ab initio</i> MD simulations. Therefore, this GEBF-ML protocol is expected to be an efficient and systematic way to build force fields for proteins and other biological systems with QM accuracy.<b></b></p>

scholarly journals Dynamic Structural Effects on the Second-Harmonic Generation of Tryptophane-Rich Peptides and Gramicidin A

2020 ◽  
Author(s):  
Jakob Seibert ◽  
Benoît CHAMPAGNE ◽  
Stefan Grimme ◽  
Marc de Wergifosse
Keyword(s):  
Second Harmonic Generation ◽  
Harmonic Generation ◽  
Density Functional ◽  
Second Harmonic ◽  
Tight Binding ◽  
Computational Cost ◽  
Conformational Space ◽  
First Hyperpolarizability ◽  
Structure Property ◽  
Tryptophan Residues

<div>Chains of amino acids can model endogenous biotags for applications in second harmonic imaging microscopy. Such structures are inherently flexible which may strongly affect their structure-property relationship. Here, we explore quantum-mechanically the conformational space of a set of relatively large tryptophan-rich model peptides studied experimentally by Duboisset et al. [JPC B 2014 118]. This has become feasible because of the recently proposed meta-dynamics method based on efficient tight-binding (TB) quantum chemical calculations. The TB version of the simplified time-dependent density functional theory (sTD-DFT-xTB) method is used to evaluate the first hyperpolarizability. These new tools enable us to calculate nonlinear optical properties for systems with several thousand atoms and/or to screen large structure ensembles. First, we show that the first hyperpolarizability of these systems is dominated by the indole chromophore in the tryptophan residues. Their relative orientation mostly determines the global β tensor and affects the static first hyperpolarizability response drastically. The results underline the importance of finding low-energy conformers for modeling the first hyperpolarizabilities of flexible molecules. Additionally, we compare calculated and extrapolated experimental static first hyperpolarizabilities. <br></div><div>We conclude that the sTD-DFT-xTB method is capable of providing reliable second-harmonic generation values for tryptophan-rich systems at a fraction of the computational cost of the commonly used TD-DFT/TD-HF levels of theory.</div>

scholarly journals Pareto Optimization of Oligomer Polarizability and Dipole Moment using a Genetic Algorithm

2021 ◽  
Author(s):  
Danielle Hiener ◽  
Geoffrey Hutchison
Keyword(s):  
Genetic Algorithm ◽  
Dipole Moment ◽  
High Performance ◽  
Density Functional ◽  
Chemical Space ◽  
Dipole Moments ◽  
Tight Binding ◽  
Dielectric Materials ◽  
Underlying Structure ◽  
Large Set

High performance electronic components are highly sought after in order to produce increasingly smaller and cheaper electronic devices. Drawing inspiration from inorganic dielectric materials, in which both polarizability and polarization contribute, organic materials can also maximize both. For a large set of small molecules drawn from PubChem, a Pareto-like front appears between polarizability and dipole moment indicating the presence of an apparent trade-off between these two properties. We tested this balance in π-conjugated materials by searching for novel conjugated hexamers with simultaneously large polarizabilities and dipole moments with potential use for dielectric materials. Using a genetic algorithm (GA) screening technique in conjunction with an approximate density functional tight binding method (GFN2-xTB) for property calculations, we were able to efficiently search chemical space for optimal hexamers. Given the scope of chemical space, using the GA technique saves considerable time and resources by speeding up molecular searches compared to a systematic search. We also explored the underlying structure-function relationships, including sequence and monomer properties, that characterize large polarizability and dipole moment regimes.

scholarly journals Spectrometric and computational studies of the binding of HIV-1 integrase inhibitors to viral DNA extremities

2019 ◽  
Vol 1 ◽  
pp. e6
Author(s):  
Léa El Khoury ◽  
Krystel El Hage ◽  
Jean-Philip Piquemal ◽  
Serge Fermandjian ◽  
Richard G. Maroun ◽  
...  
Keyword(s):  
Density Functional ◽  
Density Functional Theory Calculations ◽  
Strand Transfer ◽  
Free Energies ◽  
Resistance Mutations ◽  
Viral Dna ◽  
Functional Theory ◽  
Preferential Binding ◽  
Fluorescence Titrations ◽  
Dynamics Simulations

Three integrase strand transfer inhibitors are in intensive clinical use, raltegravir (RAL), elvitegravir (EVG) and dolutegravir (DTG). The onset of integrase resistance mutations limits their therapeutic efficiency. As put forth earlier, the drug affinity for the intasome could be improved by targeting preferentially the retroviral nucleobases, which are little, if at all, mutation-prone. We report experimental results of anisotropy fluorescence titrations of viral DNA by these three drugs. These show the DTG > EVG > RAL ranking of their inhibitory activities of the intasome to correspond to that of their free energies of binding, ∆Gs, to retroviral DNA, and that such a ranking is only governed by the binding enthalpies, ∆H, the entropy undergoing marginal variations. We sought whether this ranking might be reproduced through quantum chemistry (QC) Density Functional Theory calculations of intermolecular interaction energies between simplified models consisting of sole halobenzene ring and the highly conserved retroviral nucleobases G4 and C16. These calculations showed that binding of EVG has a small preference over DTG, while RAL ranked third. This indicates that additional interactions of the diketoacid parts of the drugs with DNA could be necessary to further enable preferential binding of DTG. The corresponding ∆Etot values computed with a polarizable molecular mechanics/dynamics procedure, Sum of Interactions Between Fragments Ab initio computed (SIBFA), showed good correlations with this ∆E(QC) ranking. These validations are an important step toward the use of polarizable molecular dynamics simulations on DTG or EVG derivatives in their complexes with the complete intasome, an application now motivated and enabled by the advent of currently developed and improved massively parallel software.

scholarly journals THEORETICAL STUDY ON THE REACTION MECHANISM OF CO2 FORMATION FROM ACYLOXY RADICALS

2018 ◽  
Vol 55 (6A) ◽  
pp. 105
Author(s):  
Nguyen Thi Minh Hue
Keyword(s):  
Reaction Mechanism ◽  
Density Functional ◽  
Basis Sets ◽  
Free Energies ◽  
Combustion Chemistry ◽  
Functional Theory ◽  
Mechanism Of Decomposition ◽  
Energy Profiles ◽  
The Density Functional Theory ◽  
Experimental Values

The decomposition mechanism of acyloxy radicals has been studied by the Density Functional Theory (DFT) using B3LYP functional in conjunction with the 6-311++G(d,p) and 6-311++G(3df,2p) basis sets. The potential energy profiles for reaction systems were generally established. Calculated results indicate that the formation of products including hydrocarbon radicals and CO2 molecule is energetically favored. The rate of decomposition increases with the number of carbon in non-cyclic saturated acyloxy radicals. Calculated enthalpies and Gibbs free energies of reactions well agree with experimental values. This study is a contribution to the understanding of the reaction mechanism of decomposition of acyloxy radicals in atmosphere and combustion chemistry. 

Nucleophilic Substitution Reactions of Cyclic Thiosulfinates Are Accelerated by Hyperconjugative Interactions

2019 ◽  
Author(s):  
Daniel Donnelly ◽  
Jeffrey Agar ◽  
Steven Lopez
Keyword(s):  
Density Functional Theory ◽  
Nucleophilic Substitution ◽  
Strain Energy ◽  
Density Functional ◽  
Density Functional Theory Calculations ◽  
Free Energies ◽  
Substitution Reactions ◽  
Functional Theory ◽  
Nucleophilic Substitution Reactions

Strain energy has been shown to promote the nucleophilic substitution reactions of cyclic disulfides, the reactivities of cyclic thiosulfinate nucleophilic substitution is unexplored. We used density functional theory calculations [M06-2X/6-311++G(d,p)] to determine the activation and reaction free energies for the reactions of 3—10-membered cyclic thiosulfinates and cyclic disulfides with methyl thiolate.

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