Evidence for cooperative Na<sup>+</sup> and Cl<sup>−</sup> binding by strongly hydrated <scp>l</scp>-proline

Dmitrieva, O.; Fedotova, M. V.; Buchner, Richard

doi:10.1039/c7cp04335j

Cited by 28 publications

(13 citation statements)

References 60 publications

(106 reference statements)

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“…Namely, the 3DRISM reduces the problem to numerical solution of Ornstein-Zernike integral equations similar to those for simple fluids. The model is very popular for treatment of small bio-rganic solutes [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ].…”

Section: Introductionmentioning

confidence: 99%

Site Density Functional Theory and Structural Bioinformatics Analysis of the SARS-CoV Spike Protein and hACE2 Complex

Tučs

Bera

et al. 2022

Molecules

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The entry of the SARS-CoV-2, a causative agent of COVID-19, into human host cells is mediated by the SARS-CoV-2 spike (S) glycoprotein, which critically depends on the formation of complexes involving the spike protein receptor-binding domain (RBD) and the human cellular membrane receptor angiotensin-converting enzyme 2 (hACE2). Using classical site density functional theory (SDFT) and structural bioinformatics methods, we investigate binding and conformational properties of these complexes and study the overlooked role of water-mediated interactions. Analysis of the three-dimensional reference interaction site model (3DRISM) of SDFT indicates that water mediated interactions in the form of additional water bridges strongly increases the binding between SARS-CoV-2 spike protein and hACE2 compared to SARS-CoV-1-hACE2 complex. By analyzing structures of SARS-CoV-2 and SARS-CoV-1, we find that the homotrimer SARS-CoV-2 S receptor-binding domain (RBD) has expanded in size, indicating large conformational change relative to SARS-CoV-1 S protein. Protomer with the up-conformational form of RBD, which binds with hACE2, exhibits stronger intermolecular interactions at the RBD-ACE2 interface, with differential distributions and the inclusion of specific H-bonds in the CoV-2 complex. Further interface analysis has shown that interfacial water promotes and stabilizes the formation of CoV-2/hACE2 complex. This interaction causes a significant structural rigidification of the spike protein, favoring proteolytic processing of the S protein for the fusion of the viral and cellular membrane. Moreover, conformational dynamics simulations of RBD motions in SARS-CoV-2 and SARS-CoV-1 point to the role in modification of the RBD dynamics and their impact on infectivity.

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Section: Introductionmentioning

confidence: 99%

Site Density Functional Theory and Structural Bioinformatics Analysis of the SARS-CoV Spike Protein and hACE2 Complex

Tučs

Bera

et al. 2022

Molecules

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“…In our study, we have performed the statistical mechanics calculations using the integral equation method of the theory of liquids in the framework of the one-dimensional (1D-) , and three-dimensional (3D-) , reference interaction site model (RISM). These approaches are intensively applied for the description of molecular and ion-molecular fluids and were found to be efficient tools in the investigation of intermolecular interactions, including ion binding in aqueous systems. ,,− …”

Section: Introductionmentioning

confidence: 99%

Ion Pairing of the Neurotransmitters Acetylcholine and Glutamate in Aqueous Solutions

Kruchinin

Fedotova

2021

J. Phys. Chem. B

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Neurotransmitters (NTs) play an important role in neural communication, regulating a variety of functions such as motivation, learning, memory, and muscle contraction. Their intermolecular interactions in biological media are an important factor affecting their biological activity. However, the available information on the features of these interactions is scarce and contradictory, especially, in an estimation of possible ion binding. In this paper, we present the results of a study for two well-known NTs, acetylcholine (ACh) and glutamate (Glu), with relation to the NT–inorganic ion and the NT–NT binding in a water environment. The features of NT pairing are investigated in aqueous AChCl and NaGlu solutions over a wide concentration range using the integral equation method in 1D- and 3D- reference interaction site model (RISM) approaches. The data for ACh are given for its two bioactive TG (trans, gauche) and TT (trans, trans) conformers. As was found, for both NTs, the results indicate the NT–inorganic counterion contact pair to be the predominant associate type in the concentrated solutions. In this case, the counterions occupy the vacated “water” space in the hydration shell of the onium moiety (ACh) or carboxylate groups (Glu). For ACh, the “unfolded” TT conformer demonstrates a slightly greater possibility for counterion pairing in comparison with the “folded” TG conformer. For Glu, the probability of its binding with a counterion is slightly stronger for the “side-chain” carboxylate group than for the “backbone” group. The obtained results also revealed an insignificant probability of Glu––Glu– pairing. Namely, the RISM data indicate Glu––Glu– binding by NH3 +–COO– interactions. A link between the ion binding of NTs and their biological activity is discussed. This contribution adds new knowledge to our understanding of the interactions between the NTs and their molecular environment, providing further insights into the behavior of these compounds in biological media.

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“…The 3D-RISM method [24][25] with the 3D-Kovalenko-Hirata closure was used to describe hydration of CoV-2/hACE2 and CoV/hACE2 complexes. These calculations describe hydration on a molecular-atom level and has proven their power in many successful studies of ion / molecule hydration, including various biocompounds [26][27][28][29][30][31][32][33][34][35][36]. In the framework of 3D-RISM theory molecule-atom spatial distribution functions are obtained.…”

Section: D Rism Calculationsmentioning

confidence: 99%

Prefusion conformation of SARS-CoV-2 receptor-binding domain favours interactions with human receptor ACE2

Tučs

Bera

et al. 2021

Preprint

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A new coronavirus epidemic COVID-19 caused by Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) poses serious threat across continents, leading to the World Health Organization declaration of a Public Health Emergence of International Concern. In order to stop the entry of the virus into human host cell, major therapeutic and vaccine design efforts are now targeting interactions between the SARS-CoV-2 spike (S) glycoprotein and the human cellular membrane receptor angiotensin-converting enzyme, hACE2. By analysing cryo-EM structures of SARS-CoV-2 and SARS-CoV-1, we report here that the homotrimer SARS-CoV-2 S receptor-binding domain (RBD) that bind with hACE2 has expanded in size with a large conformational change of its AA residues relative to SARS-CoV-1 S protein. Protomer with the up-conformational form RBD that only can bind with hACE2 showed higher intermolecular interactions at the interface, with differential distributions and the inclusion of two specific H-bonds in the CoV-2 complex. However, these interactions are resulted in significant reductions in structural rigidity, favouring proteolytic processing of S protein for the fusion of the viral and cellular membrane. Further conformational dynamics analysis of the RBD motions of SARS-CoV-2 and SARS-CoV-1 point to the role in modification in the RBD conformational dynamics and their likely impact on infectivity.

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Evidence for cooperative Na⁺ and Cl⁻ binding by strongly hydrated l-proline

Cited by 28 publications

References 60 publications

Site Density Functional Theory and Structural Bioinformatics Analysis of the SARS-CoV Spike Protein and hACE2 Complex

Site Density Functional Theory and Structural Bioinformatics Analysis of the SARS-CoV Spike Protein and hACE2 Complex

Ion Pairing of the Neurotransmitters Acetylcholine and Glutamate in Aqueous Solutions

Prefusion conformation of SARS-CoV-2 receptor-binding domain favours interactions with human receptor ACE2

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Evidence for cooperative Na+ and Cl− binding by strongly hydrated l-proline

Cited by 28 publications

References 60 publications

Site Density Functional Theory and Structural Bioinformatics Analysis of the SARS-CoV Spike Protein and hACE2 Complex

Site Density Functional Theory and Structural Bioinformatics Analysis of the SARS-CoV Spike Protein and hACE2 Complex

Ion Pairing of the Neurotransmitters Acetylcholine and Glutamate in Aqueous Solutions

Prefusion conformation of SARS-CoV-2 receptor-binding domain favours interactions with human receptor ACE2

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Evidence for cooperative Na⁺ and Cl⁻ binding by strongly hydrated l-proline