Computational Design of Miniproteins as SARS-CoV-2 Therapeutic Inhibitors

A rational therapeutic strategy is urgently needed for combating SARS-CoV-2 infection. Viral infection initiates when the SARS-CoV-2 receptor-binding domain (RBD) binds to the ACE2 receptor, and thus, inhibiting RBD is a promising therapeutic for blocking viral entry. In this study, the structure of lead antiviral candidate binder (LCB1), which has three alpha-helices (H1, H2, and H3), is used as a template to design and simulate several miniprotein RBD inhibitors. LCB1 undergoes two modifications: structural modification by truncation of the H3 to reduce its size, followed by single and double amino acid substitutions to enhance its binding with RBD. We use molecular dynamics (MD) simulations supported by ab initio density functional theory (DFT) calculations. Complete binding profiles of all miniproteins with RBD have been determined. The MD investigations reveal that the H3 truncation results in a small inhibitor with a −1.5 kcal/mol tighter binding to RBD than original LCB1, while the best miniprotein with higher binding affinity involves D17R or E11V + D17R mutation. DFT calculations provide atomic-scale details on the role of hydrogen bonding and partial charge distribution in stabilizing the minibinder:RBD complex. This study provides insights into general principles for designing potential therapeutics for SARS-CoV-2.

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γ-Valerolactone-Introduced Controlled-Isomerization of Glucose for Lactic Acid Production over Sn-Beta Catalyst

Green Chemistry ◽

10.1039/d1gc00378j ◽

2021 ◽

Author(s):

Xinpeng Zhao ◽

Zhimin Zhou ◽

hu luo ◽

Yanfei Zhang ◽

Wang Liu ◽

...

Keyword(s):

Density Functional Theory ◽

Lactic Acid ◽

Dft Calculations ◽

Acid Production ◽

Density Functional ◽

Lactic Acid Production ◽

Hydrothermal Conversion ◽

Functional Theory ◽

Environment Friendly

Combined experiments and density functional theory (DFT) calculations provided insights into the role of the environment-friendly γ-valerolactone (GVL) as a solvent in the hydrothermal conversion of glucose into lactic acid...

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DFT Studies of Graphene-Functionalised Derivatives of Capecitabine

Zeitschrift für Naturforschung A ◽

10.1515/zna-2017-0290 ◽

2017 ◽

Vol 72 (12) ◽

pp. 1131-1138 ◽

Cited By ~ 1

Author(s):

Mehdi Aramideh ◽

Mahmoud Mirzaei ◽

Ghadamali Khodarahmi ◽

Oğuz Gülseren

Keyword(s):

Density Functional ◽

Density Functional Theory Calculations ◽

Atomic Scale ◽

Phase System ◽

Molecular Models ◽

Functional Theory ◽

Atomic Properties ◽

Scale Properties ◽

Derivatives Of

AbstractCancer is one of the major problems for so many people around the world; therefore, dedicating efforts to explore efficient therapeutic methodologies is very important for researchers of life sciences. In this case, nanostructures are expected to be carriers of medicinal compounds for targeted drug design and delivery purposes. Within this work, the graphene (Gr)-functionalised derivatives of capecitabine (CAP), as a representative anticancer, have been studied based on density functional theory calculations. Two different sizes of Gr molecular models have been used for the functionalisation of CAP counterparts, CAP-Gr3 and CAP-Gr5, to explore the effects of Gr-functionalisation on the original properties of CAP. All singular and functionalised molecular models have been optimised and the molecular and atomic scale properties have been evaluated for the optimised structures. Higher formation favourability has been obtained for CAP-Gr5 in comparison with CAP-Gr3 and better structural stability has been obtained in the water-solvated system than the isolated gas-phase system for all models. The CAP-Gr5 model could play a better role of electron transferring in comparison with the CAP-Gr3 model. As a concluding remark, the molecular properties of CAP changed from singular to functionalised models whereas the atomic properties remained almost unchanged, which is expected for a carrier not to use significant perturbations to the original properties of the carried counterpart.

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Ruthenium-based catalysts for water oxidation: the key role of carboxyl groups as proton acceptors

Physical Chemistry Chemical Physics ◽

10.1039/c9cp05893a ◽

2020 ◽

Vol 22 (9) ◽

pp. 5249-5254 ◽

Cited By ~ 2

Author(s):

Yuting Liu ◽

Xiaofang Su ◽

Wei Guan ◽

Likai Yan

Keyword(s):

Density Functional Theory ◽

Dft Calculations ◽

Water Oxidation ◽

Density Functional ◽

Carboxyl Groups ◽

Functional Theory

In this work, the mechanism of water oxidation catalyzed by an Ru-based complex [Ru(L)]+ (L = 5,5-chelated 2-carboxy-phen, 2,2′;6′,2′′-terpyridine) was studied by density functional theory (DFT) calculations.

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Polydopamine and eumelanin molecular structures investigated with ab initio calculations

Chemical Science ◽

10.1039/c6sc04692d ◽

2017 ◽

Vol 8 (2) ◽

pp. 1631-1641 ◽

Cited By ~ 67

Author(s):

Chun-Teh Chen ◽

Francisco J. Martin-Martinez ◽

Gang Seob Jung ◽

Markus J. Buehler

Keyword(s):

Molecular Dynamics ◽

Density Functional Theory ◽

Dft Calculations ◽

Ab Initio Calculations ◽

Ab Initio ◽

Density Functional ◽

Md Simulations ◽

Molecular Structures ◽

Brute Force ◽

Functional Theory

A set of computational methods that contains a brute-force algorithmic generation of chemical isomers, molecular dynamics (MD) simulations, and density functional theory (DFT) calculations is reported and applied to investigate nearly 3000 probable molecular structures of polydopamine (PDA) and eumelanin.

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The Role of SiH3 Diffusion in Determining the Surface Smoothness of Plasma-Deposited Amorphous Si Thin Films: An Atomic-Scale Analysis

MRS Proceedings ◽

10.1557/proc-862-a3.2 ◽

2005 ◽

Vol 862 ◽

Author(s):

Mayur S. Valipa ◽

Tamas Bakos ◽

Eray S. Aydil ◽

Dimitrios Maroudas

Keyword(s):

Thin Films ◽

Density Functional ◽

Activation Barrier ◽

Density Functional Theory Calculations ◽

Atomic Scale ◽

Functional Theory ◽

Weak Adsorption ◽

Dynamics Simulations ◽

Hydrogenated Amorphous

AbstractDevice-quality hydrogenated amorphous silicon (a-Si:H) thin films grown under conditions where the SiH3 radical is the dominant deposition precursor are remarkably smooth, as the SiH3 radical is very mobile and fills surface valleys during its diffusion on the a-Si:H surface. In this paper, we analyze atomic-scale mechanisms of SiH3 diffusion on a-Si:H surfaces based on molecular-dynamics simulations of SiH3 radical impingement on surfaces of a-Si:H films. The computed average activation barrier for radical diffusion on a-Si:H is 0.16 eV. This low barrier is due to the weak adsorption of the radical onto the a-Si:H surface and its migration predominantly through overcoordination defects; this is consistent with our density functional theory calculations on crystalline Si surfaces. The diffusing SiH3 radical incorporates preferentially into valleys on the a-Si:H surface when it transfers an H atom and forms a Si-Si backbond, even in the absence of dangling bonds.

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Role of keto–enol tautomerization in a chiral phosphoric acid catalyzed asymmetric thiocarboxylysis of meso-epoxide: a DFT study

Organic & Biomolecular Chemistry ◽

10.1039/c5ob01473e ◽

2015 ◽

Vol 13 (45) ◽

pp. 10981-10985 ◽

Cited By ~ 14

Author(s):

Manjaly J. Ajitha ◽

Kuo-Wei Huang

Keyword(s):

Density Functional Theory ◽

Phosphoric Acid ◽

Dft Calculations ◽

Density Functional ◽

Dft Study ◽

Functional Theory ◽

Chiral Phosphoric Acid ◽

Acid Catalyzed

The mechanism of a chiral phosphoric acid catalyzed thiocarboxylysis of meso-epoxide was investigated by density functional theory (DFT) calculations (M06-2X).

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The Role of Oxygenic Groups and Sp3 Carbon Hybridization in Activated Graphite Electrodes for Vanadium Redox Flow Batteries

10.26434/chemrxiv.14546847 ◽

2021 ◽

Author(s):

Ali Hassan ◽

Asnake Sahele Haile ◽

Theodore Tzedakis ◽

Heine Anton Hansen ◽

Piotr de Silva

Keyword(s):

Dft Calculations ◽

Density Functional ◽

Vanadium Redox Flow Battery ◽

Carbon Surface ◽

Graphite Electrodes ◽

Functional Theory ◽

Redox Flow Batteries ◽

Flow Batteries ◽

Vanadium Redox

Graphite felt is a widely used electrode material for vanadium redox flow batteries. Electrode activation leads to the functionalization of the graphite surface with epoxy, OH, C=O, and COOH oxygenic groups and changes the carbon surface morphology and electronic structure; thus, improving the electrode’s electroactivity relative to the untreated graphite. In this study, we conduct density functional theory (DFT) calculations to evaluate functionalization’s role towards the positive half-cell reaction of the vanadium redox flow battery. The DFT calculations show that oxygenic groups improve the graphite felt’s affinity towards the VO2+/VO2+ redox couple in the following order: C=O > COOH > OH > basal plane. Projected density of states (PDOS) calculations show that these groups increase the electrode’s sp3 hybridization in the same order. We conclude that the increase in the sp3 hybridization is responsible for the improved electroactivity, while the oxygenic groups’ presence is responsible for this sp3 increment. These insights can help in the better selection of activation processes and optimization of their parameters.

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Simulating Surfactant-Iron Oxide Interfaces: From Density Functional Theory to Molecular Dynamics

10.26434/chemrxiv.8325356 ◽

2019 ◽

Author(s):

Carlos Ayestaran Latorre ◽

James Ewen ◽

Chiara Gattinoni ◽

Daniele Dini

Keyword(s):

Molecular Dynamics ◽

Density Functional Theory ◽

Iron Oxide ◽

Dft Calculations ◽

Density Functional ◽

Md Simulations ◽

Oxide Surfaces ◽

Interaction Energies ◽

Functional Theory ◽

Oxide Interfaces

<div>Understanding the behaviour of surfactant molecules on iron oxide surfaces is important for many industrial applications. Molecular dynamics (MD) simulations of such systems have been limited by the absence of a force-feild (FF) which accurately describes the molecule-surface interactions. In this study, interaction energies from density functional theory (DFT) + U calculations with a van der Waals functional are used to parameterize a classical FF for MD simulations of amide surfactants on iron oxide surfaces. The Original FF, which was derived using mixing rules and surface Lennard-Jones (LJ) parameters developed for nonpolar molecules, were shown to signi cantly underestimate the adsorption energy and overestimate the equilibrium adsorption distance compared to DFT. Conversely, the Optimized FF showed excellent agreement with the interaction energies obtained from DFT calculations for a wide range of surface coverages and molecular conformations near to and adsorbed on a-Fe2O3(0001). This was facilitated through the use of a Morse potential for strong chemisorption interactions, modi fied LJ parameters for weaker physisorption interactions, and adjusted partial charges for the electrostatic interactions. The Original FF and Optimized FF were compared in classical nonequilibrium molecular dynamics (NEMD) simulations of amide molecules con fined between iron oxide surfaces. When the Optimized FF was employed, the amide molecules were pulled closer to the surface and the orientation of the headgroups was more similar to that observed in the DFT calculations compared to the Original FF. The Optimized FF proposed here facilitates classical MD simulations of amide-iron oxide interfaces in which the interactions are representative of accurate DFT calculations.</div>

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How easy is CO2 fixation by M–C bond containing complexes (M = Cu, Ni, Co, Rh, Ir)?

Organic Chemistry Frontiers ◽

10.1039/c5qo00281h ◽

2016 ◽

Vol 3 (1) ◽

pp. 19-23 ◽

Cited By ~ 14

Author(s):

Sai V. C. Vummaleti ◽

Giovanni Talarico ◽

Steven P. Nolan ◽

Luigi Cavallo ◽

Albert Poater

Keyword(s):

Density Functional Theory ◽

Dft Calculations ◽

Density Functional ◽

Co2 Fixation ◽

Functional Theory

A comparison between different M–C bonds (M = Cu(i), Ni(ii), Co(i), Rh(i) and Ir(i)) has been reported by using density functional theory (DFT) calculations to explore the role of the metal in the fixation or incorporation of CO2 into such complexes.

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An insight into methanol oxidation mechanisms on RuO2(100) under an aqueous environment by DFT calculations

Physical Chemistry Chemical Physics ◽

10.1039/c6cp08522a ◽

2017 ◽

Vol 19 (11) ◽

pp. 7476-7480 ◽

Cited By ~ 9

Author(s):

Tian Sheng ◽

Jin-Yu Ye ◽

Wen-Feng Lin ◽

Shi-Gang Sun

Keyword(s):

Dft Calculations ◽

Methanol Oxidation ◽

Density Functional ◽

Md Simulations ◽

Water Molecules ◽

Aqueous Environment ◽

Interfacial Water ◽

Functional Theory ◽

Oxidation Mechanisms ◽

Insight Into

In this work, we have studied methanol oxidation mechanisms on RuO2(100) by using density functional theory (DFT) calculations and ab initio molecular dynamics (MD) simulations with some explicit interfacial water molecules.

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