scholarly journals Solution and gas-phase modifiers effect on heme proteins environment and conformational space

2018 ◽  
Author(s):  
D. Butcher ◽  
J. Miksovska ◽  
M. E. Ridgeway ◽  
M. A. Park ◽  
F. Fernandez-Lima
Keyword(s):  
Gas Phase ◽  
Ion Mobility ◽  
Heme Proteins ◽  
Organic Molecules ◽  
Tertiary Structure ◽  
Organic Content ◽  
Conformational Space ◽  
Starting Solution ◽  
Trapped Ion Mobility Spectrometry ◽  
Secondary And Tertiary Structure

AbstractThe molecular environment is known to impact the secondary and tertiary structure of biomolecules, shifting the equilibrium between different conformational and oligomerization states. In the present study, the effect of solution additives and gas-phase modifiers on the molecular environment of two common heme proteins, bovine cytochrome c and equine myoglobin, is investigated as a function of the time after desolvation (e.g., 100 - 500 ms) using trapped ion mobility spectrometry – mass spectrometry. Changes in the mobility profiles are observed depending on the starting solution composition (i.e., in aqueous solution at neutral pH or in the presence of organic content: methanol, acetone, or acetonitrile) depending on the protein. In the presence of gas-phase modifiers (i.e., N2 containing methanol, acetone, or acetonitrile), a shift in the mobility profiles driven by the gas-modifier mass and size and changes in the relative abundances and number of IMS bands are observed. We attribute these changes in the mobility profiles in the presence of gas-phase modifiers to a clustering/declustering mechanism by which organic molecules adsorb to the protein ion surface and lower energetic barriers for interconversion between conformational states, thus redefining the free energy landscape and equilibria between conformers. These structural biology experiments open new avenues for manipulation and interrogation of biomolecules in the gas-phase with the potential to emulate a large suite of solution conditions, ultimately including conditions that more accurately reflect a variety of intracellular environments.

scholarly journals The effects of solution additives and gas‐phase modifiers on the molecular environment and conformational space of common heme proteins

2019 ◽  
Vol 33 (5) ◽  
pp. 399-404 ◽  
Author(s):  
David Butcher ◽  
Jaroslava Miksovska ◽  
Mark E. Ridgeway ◽  
Melvin A. Park ◽  
Francisco Fernandez‐Lima
Keyword(s):  
Gas Phase ◽  
Heme Proteins ◽  
Conformational Space

Effect of Antioxidants on Heavy Metals Induced Conformational Altera-tion of Cytochrome C And Myoglobin

2020 ◽  
Vol 27 ◽  
Author(s):  
Anwar Ahmed ◽  
Khadega Khamis Moh Alazoumi ◽  
Salman Freeh Alamery ◽  
Anas Shamsi ◽  
Basir Ahmad ◽  
...  
Keyword(s):  
Heavy Metals ◽  
Heavy Metal ◽  
Cytochrome C ◽  
Peroxidase Activity ◽  
Heme Proteins ◽  
Deleterious Effect ◽  
Tertiary Structure ◽  
Animal Origin ◽  
Metal Exposure ◽  
Secondary And Tertiary Structure

Background: The exposure to heavy metals due to unrestrained industrialization, pollution and non-degradability imposes a significant risk to human health. Proteins are prime targets of heavy metal stress, however, the underlying mechanisms and its impact on heme proteins is still not entirely clear. Objective: To analyze the deleterious effect of heavy metals such as cadmium, chromium and mercury on conformation of two proteins namely, cytochrome c and myoglobin. The protective effect of glycine and ascorbic acid (animal origin), gallic acid and sesamol (plant origin) on heavy metal exposure was studied. Methods: Far- and near-UV circular dichroism (CD) measurements monitored the changes in secondary and tertiary structure. Absorption Soret spectroscopy study revealed changes in heme-protein interaction. Peroxidase activity has been assayed to measure the absorption of tetraguaiacol. The interaction of heme proteins with different heavy metals was done using docking study. Result: Far- and near–UV CD measurements reveal that heavy metals disrupt the secondary and tertiary structure of heme proteins. Antioxidants counteract the deleterious effect of heavy metals. Absorption spectroscopy revealed changes in the Soret region of these heme proteins. Changes in peroxidase activity was observed on addition of heavy metals and antioxidants. Molecular docking validated interaction of the heavy metals with proteins with a significant binding affinity (-2.3 kcal/mol). Conclusion: Heavy metals interfered and disrupted both the heme proteins and mercury showed the maximum deleterious effect, further, chromium showed detrimental effect at very small concentration. The antioxidants from animal origin exhibited better protective response than those from plant source.

scholarly journals Modeling the Thermodynamics of Conformational Isomerism in Solution via Unsupervised Clustering: The Case of Sildenafil

2020 ◽  
Author(s):  
Veselina Marinova ◽  
Laurence Dodd ◽  
Song-Jun Lee ◽  
Geoffrey P. F. Wood ◽  
Ivan Marziano ◽  
...  
Keyword(s):  
Gas Phase ◽  
Degrees Of Freedom ◽  
Systematic Approach ◽  
Organic Molecules ◽  
Unsupervised Clustering ◽  
Conformational Space ◽  
Energetic Cost ◽  
Conformational Ensemble ◽  
Density Peaks ◽  
Crystal Bulk

<p>We present a systematic approach for the identification of statistically relevant conformational macrostates of organic molecules from molecular dynamics trajectories. The approach applies to molecules characterised by an arbitrary number of torsional degrees of freedom and enables the transferability of the macrostates definition across different environments. We formulate a dissimilarity measure between molecular configurations that incorporates information on the characteristic energetic cost associated with transitions along all relevant torsional degrees of freedom. Such metric is employed to perform unsupervised clustering of molecular configurations based on the fast search and find of density peaks algorithm. We apply this method to investigate the equilibrium conformational ensemble of Sildenafil, a conformationally complex pharmaceutical compound, in different environments including the crystal bulk, the gas phase and three different solvents (acetonitrile, 1-butanol, and toluene). We demonstrate that, while Sildenafil can adopt more than one hundred metastable conformational configurations, only 12 are significantly populated across all the environments investigated. Despite the complexity of the conformational space, we find that the most abundant conformers in solution are the closest to the conformers found in the most common Sildenafil crystal phase.</p>

scholarly journals Modeling the Thermodynamics of Conformational Isomerism in Solution via Unsupervised Clustering: The Case of Sildenafil

2020 ◽  
Author(s):  
Veselina Marinova ◽  
Laurence Dodd ◽  
Song-Jun Lee ◽  
Geoffrey P. F. Wood ◽  
Ivan Marziano ◽  
...  
Keyword(s):  
Gas Phase ◽  
Degrees Of Freedom ◽  
Systematic Approach ◽  
Organic Molecules ◽  
Unsupervised Clustering ◽  
Conformational Space ◽  
Energetic Cost ◽  
Conformational Ensemble ◽  
Density Peaks ◽  
Crystal Bulk

<p>We present a systematic approach for the identification of statistically relevant conformational macrostates of organic molecules from molecular dynamics trajectories. The approach applies to molecules characterised by an arbitrary number of torsional degrees of freedom and enables the transferability of the macrostates definition across different environments. We formulate a dissimilarity measure between molecular configurations that incorporates information on the characteristic energetic cost associated with transitions along all relevant torsional degrees of freedom. Such metric is employed to perform unsupervised clustering of molecular configurations based on the fast search and find of density peaks algorithm. We apply this method to investigate the equilibrium conformational ensemble of Sildenafil, a conformationally complex pharmaceutical compound, in different environments including the crystal bulk, the gas phase and three different solvents (acetonitrile, 1-butanol, and toluene). We demonstrate that, while Sildenafil can adopt more than one hundred metastable conformational configurations, only 12 are significantly populated across all the environments investigated. Despite the complexity of the conformational space, we find that the most abundant conformers in solution are the closest to the conformers found in the most common Sildenafil crystal phase.</p>

scholarly journals From Compact to String—The Role of Secondary and Tertiary Structure in Charge-Induced Unzipping of Gas-Phase Proteins

2016 ◽  
Vol 28 (4) ◽  
pp. 638-646 ◽  
Author(s):  
Stephan Warnke ◽  
Waldemar Hoffmann ◽  
Jongcheol Seo ◽  
Erwin De Genst ◽  
Gert von Helden ◽  
...  
Keyword(s):  
Gas Phase ◽  
Tertiary Structure ◽  
Secondary And Tertiary Structure

Implications of Blanc’s Law for Use in Trapped Ion Mobility Spectrometry

2021 ◽  
Author(s):  
Cameron N. Naylor ◽  
Tobias Reinecke ◽  
Mark E. Ridgeway ◽  
Melvin A. Park ◽  
Brian H. Clowers
Keyword(s):  
Ion Mobility Spectrometry ◽  
Ion Mobility ◽  
Trapped Ion ◽  
Trapped Ion Mobility Spectrometry
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