Molecular dynamics simulations and Gaussian network model for designing antibody mimicking protein towards dengue envelope protein

2021 ◽  
pp. 118086
Author(s):  
Wei Lim Chong ◽  
Visit Vao-soongnern ◽  
Piyarat Nimmanpipug ◽  
Chatchai Tayapiwatana ◽  
Jung-Hsin Lin ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Network Model ◽  
Envelope Protein ◽  
Gaussian Network Model ◽  
Dynamics Simulations ◽  
Gaussian Network

scholarly journals Causality, Transfer Entropy and Allosteric Communication Landscapes in Proteins with Harmonic Interactions

2016 ◽  
Author(s):  
Aysima Hacisuleyman ◽  
Burak Erman
Keyword(s):  
Network Model ◽  
Protein Function ◽  
Information Transfer ◽  
Protein Activity ◽  
Additional Information ◽  
Gaussian Network Model ◽  
Allosteric Communication ◽  
Rapid Characterization ◽  
Dynamics Simulations ◽  
Gaussian Network

AbstractA fast and approximate method of generating allosteric communication landscapes is presented by using Schreiber's entropy transfer concept in combination with the Gaussian Network Model of proteins. Predictions of the model and the allosteric communication landscapes generated show that information transfer in proteins does not necessarily take place along a single path, but through an ensemble of pathways. The model emphasizes that knowledge of entropy only is not sufficient for determining allosteric communication and additional information based on time delayed correlations has to be introduced, which leads to the presence of causality in proteins. The model provides a simple tool for mapping entropy sink-source relations into pairs of residues. Residues that should be manipulated to control protein activity may be determined with this approach. This should be of great importance for allosteric drug design and for understanding the effects of mutations on protein function. The model is applied to determine allosteric communication in two proteins, Ubiquitin and Pyruvate Kinase. Predictions are in agreement with detailed molecular dynamics simulations and experimental evidence.SignificanceProteins perform their function by an exchange of information within themselves and with their environments through correlated fluctuations of their atoms. Fluctuations of one atom may drive the fluctuations of another. Information transmitted in this way leads to allosteric communication which is described as the process in which action at one site of the protein is transmitted to another site at which the protein performs its activity. Disruption of allosteric communication by mutation for example leads to disease. The present paper incorporates information theoretic concepts into the well known Gaussian Network Model of proteins and allows for rapid characterization of allosteric communication landscapes for normal functioning as well as malfunctioning proteins.

scholarly journals A modified random network model for P2O5–Na2O–Al2O3–SiO2 glass studied by molecular dynamics simulations

RSC Advances ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 7025-7036
Author(s):  
Yaxian Zhao ◽  
Jincheng Du ◽  
Xin Cao ◽  
Chong Zhang ◽  
Gang Xu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Network Model ◽  
Structural Model ◽  
Random Network ◽  
Sio2 Glass ◽  
Sodium Aluminosilicate ◽  
Aluminosilicate Glasses ◽  
Dynamics Simulations ◽  
Glass Compositions

(A) A modified structural model proposed for P2O5-bearing sodium aluminosilicate glasses. (B) Degree of preferred connection (DPC) of different T–O–T network linkage for LAP, MAP and HAP glass compositions with various P2O5 content.

scholarly journals Virtual Repurposing of Ursodeoxycholate and Chenodeoxycholate as Lead Candidates Against SARS-Cov2-Envelope Protein: A Molecular Dynamics Investigation

2020 ◽  
Author(s):  
Reena Yadav ◽  
chinmayee choudhury ◽  
Yashwant Kumar ◽  
Alka Bhatia
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulations ◽  
Envelope Protein ◽  
Homology Modelling ◽  
Protein A ◽  
Drug Repurposing ◽  
Dynamics Simulations ◽  
Global Threat ◽  
Polar Functional Groups

Drug repurposing is an apt choice to combat the currently prevailing global threat of COVID-19, caused by SARS-Cov2 in absence of any specific medication/vaccine. The present work attempts to computationally evaluate binding affinities and effect of two widely used surfactant drugs i.e. chenodeoxycholate (CDC) and ursodeoxycholate (UDC) with the envelope protein of SARS-Cov2 (SARS-Cov2-E) using homology modelling, molecular docking and molecular dynamics simulations. A good quality homo-pentameric structure of SARS-Cov2-E was modelled from its homologue with more than 90% sequence identity followed by symmetric docking. The pentameric structure was embedded in a DPPC membrane and subsequently energy minimized. The minimized structure was used for blind molecular docking of CDC and UDC to obtain the best scoring SARS-Cov2-E–CDC/UDC complexes, which were subjected to 230ns molecular dynamics simulations in triplicates in DPPC membrane environment. Comparative analyses of structural and enthalpic properties and molecular interaction profiles from the MD trajectories revealed that, both CDC and UDC could stably bind to SARS-Cov2-E through H-bonds, water-bridges and hydrophobic contacts in the transmembraneresidues.T30 was observed to be a key residue for CDC/UDC binding. The polar functional groups of the bound CDC/UDC facilitated entry of a large number of water molecules into the channel and affected the H-bonding pattern between adjacent monomeric chains, loosening the compact transmembrane region of SARS-Cov2-E. These observations suggest the potential of CDC/UDC as repurposed candidates to hinder the survival of SARS-Cov2 by disrupting the structure of SARS-Cov2-E and facilitate entry of solvents/polar inhibitors inside the viral cell.

scholarly journals Virtual Repurposing of Ursodeoxycholate and Chenodeoxycholate as Lead Candidates Against SARS-Cov2-Envelope Protein: A Molecular Dynamics Investigation

2020 ◽  
Author(s):  
Reena Yadav ◽  
chinmayee choudhury ◽  
Yashwant Kumar ◽  
Alka Bhatia
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulations ◽  
Envelope Protein ◽  
Homology Modelling ◽  
Protein A ◽  
Drug Repurposing ◽  
Dynamics Simulations ◽  
Global Threat ◽  
Polar Functional Groups

Drug repurposing is an apt choice to combat the currently prevailing global threat of COVID-19, caused by SARS-Cov2 in absence of any specific medication/vaccine. The present work attempts to computationally evaluate binding affinities and effect of two widely used surfactant drugs i.e. chenodeoxycholate (CDC) and ursodeoxycholate (UDC) with the envelope protein of SARS-Cov2 (SARS-Cov2-E) using homology modelling, molecular docking and molecular dynamics simulations. A good quality homo-pentameric structure of SARS-Cov2-E was modelled from its homologue with more than 90% sequence identity followed by symmetric docking. The pentameric structure was embedded in a DPPC membrane and subsequently energy minimized. The minimized structure was used for blind molecular docking of CDC and UDC to obtain the best scoring SARS-Cov2-E–CDC/UDC complexes, which were subjected to 230ns molecular dynamics simulations in triplicates in DPPC membrane environment. Comparative analyses of structural and enthalpic properties and molecular interaction profiles from the MD trajectories revealed that, both CDC and UDC could stably bind to SARS-Cov2-E through H-bonds, water-bridges and hydrophobic contacts in the transmembraneresidues.T30 was observed to be a key residue for CDC/UDC binding. The polar functional groups of the bound CDC/UDC facilitated entry of a large number of water molecules into the channel and affected the H-bonding pattern between adjacent monomeric chains, loosening the compact transmembrane region of SARS-Cov2-E. These observations suggest the potential of CDC/UDC as repurposed candidates to hinder the survival of SARS-Cov2 by disrupting the structure of SARS-Cov2-E and facilitate entry of solvents/polar inhibitors inside the viral cell.

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