scholarly journals The binding mechanism, multiple binding modes, and allosteric regulation ofStaphylococcus aureusSortase A probed by molecular dynamics simulations

2012 ◽  
Vol 21 (12) ◽  
pp. 1858-1871 ◽  
Author(s):  
Kalli Kappel ◽  
Jeff Wereszczynski ◽  
Robert T. Clubb ◽  
J. Andrew McCammon
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Allosteric Regulation ◽  
Binding Modes ◽  
Binding Mechanism ◽  
Multiple Binding ◽  
Dynamics Simulations

Effects of Arginine on Multimodal Chromatography: Experiments and Simulations

2018 ◽  
Vol 20 (1) ◽  
pp. 40-48 ◽  
Author(s):  
Atsushi Hirano ◽  
Kentaro Shiraki ◽  
Tomoshi Kameda
Keyword(s):  
Molecular Dynamics ◽  
Mixed Mode ◽  
Binding Modes ◽  
Aromatic Residues ◽  
Multimodal Chromatography ◽  
Cationic Resin ◽  
Multiple Binding ◽  
Guanidinium Group ◽  
Dynamics Simulations ◽  
Protein Denaturant

Multimodal or mixed-mode chromatography can be used to separate various proteins, including antibodies. The separation quality and efficiency have been improved by the addition of solutes, especially arginine. This review summarizes the mechanism underlying the effects of arginine on protein elution in multimodal chromatography with neutral, anionic or cationic resin ligands; the mechanism has been investigated using experiments and molecular dynamics simulations. Arginine is effective in facilitating protein elution compared to salts and protein denaturants such as guanidine and urea. The unique elution effect of arginine can be explained by the interplay among arginine, proteins and the resin ligands. Arginine exhibits multiple binding modes for the ligands and further affinity for protein aromatic residues through its guanidinium group. These properties make arginine versatile for protein elution in multimodal chromatography. Taking into account that arginine is an aggregation suppressor for proteins but not a protein denaturant, arginine is a promising protein-eluting reagent for multimodal chromatography.

Probing the binding mechanism of polybrominated diphenyl ethers with transthyretin by multi-spectroscopic and molecular dynamics simulations

2017 ◽  
Vol 9 (26) ◽  
pp. 3929-3940 ◽  
Author(s):  
Jie Xu ◽  
Zhongsheng Yi ◽  
Yuchen Wei ◽  
Wu Yang ◽  
Lulu Yang ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Polybrominated Diphenyl Ethers ◽  
Chemical Properties ◽  
Physical And Chemical Properties ◽  
Binding Mechanism ◽  
Diphenyl Ethers ◽  
Dynamics Simulations ◽  
Physical And Chemical ◽  
And Chemical Properties

The physical and chemical properties of polybrominated diphenyl ethers (PBDEs) are important for modeling their transport.

Allosteric pathway identification through network analysis: from molecular dynamics simulations to interactive 2D and 3D graphs

2014 ◽  
Vol 169 ◽  
pp. 303-321 ◽  
Author(s):  
Ariane Allain ◽  
Isaure Chauvot de Beauchêne ◽  
Florent Langenfeld ◽  
Yann Guarracino ◽  
Elodie Laine ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Network Analysis ◽  
Molecular Dynamics Simulations ◽  
Large Scale ◽  
Allosteric Regulation ◽  
Local Perturbation ◽  
Modular Network ◽  
Allosteric Coupling ◽  
Dynamics Simulations

Allostery is a universal phenomenon that couples the information induced by a local perturbation (effector) in a protein to spatially distant regulated sites. Such an event can be described in terms of a large scale transmission of information (communication) through a dynamic coupling between structurally rigid (minimally frustrated) and plastic (locally frustrated) clusters of residues. To elaborate a rational description of allosteric coupling, we propose an original approach – MOdular NETwork Analysis (MONETA) – based on the analysis of inter-residue dynamical correlations to localize the propagation of both structural and dynamical effects of a perturbation throughout a protein structure. MONETA uses inter-residue cross-correlations and commute times computed from molecular dynamics simulations and a topological description of a protein to build a modular network representation composed of clusters of residues (dynamic segments) linked together by chains of residues (communication pathways). MONETA provides a brand new direct and simple visualization of protein allosteric communication. A GEPHI module implemented in the MONETA package allows the generation of 2D graphs of the communication network. An interactive PyMOL plugin permits drawing of the communication pathways between chosen protein fragments or residues on a 3D representation. MONETA is a powerful tool for on-the-fly display of communication networks in proteins. We applied MONETA for the analysis of communication pathways (i) between the main regulatory fragments of receptors tyrosine kinases (RTKs), KIT and CSF-1R, in the native and mutated states and (ii) in proteins STAT5 (STAT5a and STAT5b) in the phosphorylated and the unphosphorylated forms. The description of the physical support for allosteric coupling by MONETA allowed a comparison of the mechanisms of (a) constitutive activation induced by equivalent mutations in two RTKs and (b) allosteric regulation in the activated and non-activated STAT5 proteins. Our theoretical prediction based on results obtained with MONETA was validated for KIT by in vitro experiments. MONETA is a versatile analytical and visualization tool entirely devoted to the understanding of the functioning/malfunctioning of allosteric regulation in proteins – a crucial basis to guide the discovery of next-generation allosteric drugs.

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