Using the Relative Energy Gradient Method with Interacting Quantum Atoms to Determine the Reaction Mechanism and Catalytic Effects in the Peptide Hydrolysis in HIV‐1 Protease

Thacker, Joseph C. R.; Vincent, Mark A.; Popelier, Paul L. A.

doi:10.1002/chem.201802035

Cited by 35 publications

(37 citation statements)

References 73 publications

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“…The IQA partitioning scheme is an attractive candidate to serve as a bridge between chemical insight and present‐day wavefunctions. A combination of IQA and the newly proposed Relative Energy Gradient (REG) method has delivered crisp chemical insight explaining the chemical nature of a traditional hydrogen bond, enzymatic hydrolysis, the fluorine gauche effect and the origin of rotation barriers in biphenyl . IQA provides four types of energy, which are all well‐defined at atomistic level: intra‐atomic energy (which we showed corresponds to sterics), electrostatic energy (with a link to multipole moments), exchange energy (related to bond order) and correlation energy (expanding dispersion).…”

Section: Introductionmentioning

confidence: 99%

Does the Intra‐Atomic Deformation Energy of Interacting Quantum Atoms Represent Steric Energy?

et al. 2019

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We show that the mutual, through‐space compression of atomic volume experienced by approaching topological atoms causes an exponential increase in the intra‐atomic energy of those atoms, regardless of approach orientation. This insight was obtained using the modern energy partitioning method called interacting quantum atoms (IQA). This behaviour is consistent for all atoms except hydrogen, which can behave differently depending on its environment. Whilst all atoms experience charge transfer when they interact, the intra‐atomic energy of the hydrogen atom is more vulnerable to these changes than larger atoms. The difference in behaviour is found to be due to hydrogen's lack of a core of electrons, which, in heavier atoms, consistently provide repulsion when compressed. As such, hydrogen atoms do not always provide steric hindrance. In accounting for hydrogen's unusual behaviour and demonstrating the exponential character of the intra‐atomic energy in all other atoms, we provide evidence for IQA's intra‐atomic energy as a quantitative description of steric energy.

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Section: Introductionmentioning

confidence: 99%

Does the Intra‐Atomic Deformation Energy of Interacting Quantum Atoms Represent Steric Energy?

et al. 2019

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“…Since IQA offers a large number of energy terms contributing to the total energy of the complex, we used the Relative Energy Gradient (REG) method to rank these components and find the term(s) that best describe the total behavior of the system. Recently, the REG method has been successfully used to detect the most important energy terms that describe the hydrogen bond in the water dimer, the cause of the fluorine gauche effect, some S N 2 model reactions, and catalytic effects in the peptide hydrolysis in HIV‐1 Protease . Here the REG method will be used to analyze the angular behavior of IQA terms and find those that control the directionality of halogen bonded complexes.…”

Section: Introductionmentioning

confidence: 99%

Directionality of Halogen Bonds: An Interacting Quantum Atoms (IQA) and Relative Energy Gradient (REG) Study

et al. 2019

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Interacting Quantum Atoms (IQA) and Interacting Quantum Fragments (IQF) analyses are used to study normalF3C-X⋯NnormalH3 (X=Cl and Br) model complexes in order to determine the origin of halogen bond directionality. IQA allows for the calculation of intra‐ and interatomic classical and exchange‐correlation energies, which can be used to determine the energetic nature of the changes that occur when deviating from the preferred halogen bond approach. The Relative Energy Gradient (REG) method is also applied to rank the IQA energies and reveal which energy contributions best describe the total behavior of the system. Indeed, all the pairwise interactions and atomic self‐energies are angularly dependent; some terms favor the linear structure and some tend toward nonlinear arrangements. For instance, when the C−X−N angle is altered, the halogen‐nitrogen interaction energy behaves like the total energy of the system while the carbon‐nitrogen interaction works against the total energy profile. Furthermore, the REG values reveal that the contribution of the halogen‐nitrogen interaction to the total behavior of the system is small. Instead, the secondary interactions (e. g., fluorine‐nitrogen and carbon‐hydrogen interactions) and atomic self‐energies are mainly responsible for the angular preference of these halogen bonds. Finally, IQF calculations followed by REG analysis reveal the importance of the self‐energy of the fragments.

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“…This method has already been applied successfully by Popelier et al. for gaining insight into the fluorine gauche effect, the rotational barrier in biphenyl and other problems . In passing, it is noteworthy that their statement “much chemical insight ultimately comes down to finding out which fragment of a total system behaves like the total system, in terms of an energy profile” is also pertinent to molecular balances, since they are designed to dissect out a single noncovalent interaction defining the behaviour of the molecule as a whole.…”

Section: Discussionmentioning

confidence: 99%

Some Recent Advances in the Design and Use of Molecular Balances for the Experimental Quantification of Intramolecular Noncovalent Interactions of π Systems

Aliev

Motherwell

2019

Chemistry A European J

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Herein, various molecular balances used for comparing the strengths of intramolecular noncovalent interactions are reviewed. Our overview indicates that considerable quantitative insight into the strength of noncovalent interactions can be gained through the careful design of molecular balances. Many exciting opportunities certainly exist for the design of further new balances to quantify and dissect the relative strengths of noncovalent interactions as a function of solvation and the importance of the many factors that contribute to overall molecular recognition. However, even simple model molecules can show a multiplicity of intramolecular noncovalent interactions acting in a combined fashion. It is therefore essential to undertake a detailed computational analysis to identify all possible noncovalent interactions present in a selected molecular balance prior to a quantitative experimental assessment of the strength of a particular noncovalent interaction. It is also argued that the words “torsion” and “molecular balance” seem to have become inextricably linked and, in consequence, even top pan and seesaw balances have been mistakenly referred to in these terms.

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Using the Relative Energy Gradient Method with Interacting Quantum Atoms to Determine the Reaction Mechanism and Catalytic Effects in the Peptide Hydrolysis in HIV‐1 Protease

Cited by 35 publications

References 73 publications

Does the Intra‐Atomic Deformation Energy of Interacting Quantum Atoms Represent Steric Energy?

Does the Intra‐Atomic Deformation Energy of Interacting Quantum Atoms Represent Steric Energy?

Directionality of Halogen Bonds: An Interacting Quantum Atoms (IQA) and Relative Energy Gradient (REG) Study

Some Recent Advances in the Design and Use of Molecular Balances for the Experimental Quantification of Intramolecular Noncovalent Interactions of π Systems

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