scholarly journals WT and A53T α-Synuclein Systems: Melting Diagram and Its New Interpretation

2020 ◽  
Vol 21 (11) ◽  
pp. 3997 ◽  
Author(s):  
Mónika Bokor ◽  
Ágnes Tantos ◽  
Péter Tompa ◽  
Kyou-Hoon Han ◽  
Kálmán Tompa
Keyword(s):  
Hydration Shell ◽  
Structural Disorder ◽  
Random Coil ◽  
Hydration Water ◽  
Water Binding ◽  
Essential Information ◽  
Potential Barriers ◽  
Intrinsically Disordered ◽  
Accessible Surface ◽  
Solvent Accessible Surface

The potential barriers governing the motions of α-synuclein (αS) variants’ hydration water, especially energetics of them, is in the focus of the work. The thermodynamical approach yielded essential information about distributions and heights of the potential barriers. The proteins’ structural disorder was measured by ratios of heterogeneous water-binding interfaces. They showed the αS monomers, oligomers and amyloids to possess secondary structural elements, although monomers are intrinsically disordered. Despite their disordered nature, monomers have 33% secondary structure, and therefore they are more compact than a random coil. At the lowest potential barriers with mobile hydration water, monomers are already functional, a monolayer of mobile hydration water is surrounding them. Monomers realize all possible hydrogen bonds with the solvent water. αS oligomers and amyloids have half of the mobile hydration water amount than monomers because aggregation involves less mobile hydration. The solvent-accessible surface of the oligomers is ordered or homogenous in its interactions with water to 66%. As a contrast, αS amyloids are disordered or heterogeneous to 75% of their solvent accessible surface and both wild type and A53T amyloids show identical, low-level hydration. Mobile water molecules in the first hydration shell of amyloids are the weakest bound compared to other forms.

scholarly journals WT and A53T α-synuclein systems: Melting Diagram and its new interpretation

2019 ◽  
Author(s):  
M. Bokor ◽  
Á. Tantos ◽  
P. Tompa ◽  
K.-H. Han ◽  
K. Tompa
Keyword(s):  
Secondary Structure ◽  
Structural Disorder ◽  
Water Molecules ◽  
Hydration Water ◽  
Wild Type ◽  
Water Binding ◽  
Potential Barriers ◽  
Intrinsically Disordered ◽  
Mobile Water ◽  
Binding Interfaces

AbstractParkinson’s disease is connected with abnormal α-synuclein (αS) aggregation. Energetics of potential barriers governing motions of hydration water is examined. Information about the distributions and heights of potential barriers is gained by a thermodynamical approach. The ratios of the heterogeneous water-binding interfaces measure proteins’ structural disorder. All αS forms possess secondary structural elements though they are intrinsically disordered. Monomers are functional at the lowest potential barriers, where mobile hydration water exists, with monolayer coverage of mobile hydration. The αS monomer contains 33% secondary structure and is more compact than a random coil. A53T αS monomer has a more open structure than the wild type. Monomers realize all possible hydrogen bonds. Half of the mobile hydration water amount for monomers is missing in αS oligomers and αS amyloids. Oligomers are ordered by 66%. Mobile water molecules in the first hydration shell of amyloids are the weakest bound compared to other forms. Wild type and A53T amyloids show identical, low-level hydration, and are considered as disordered to 75%.Statement of SignificanceAggregation of α-synuclein into oligomers, amyloid fibrils is a hallmark of Parkinson’s disease. A thermodynamic approach provides information on the heterogeneity of protein-water bonds in the wild type and A53T mutant monomers, oligomers, amyloids. This information can be related to ratios of heterogeneous water-binding interfaces, which measure the proteins’ structural disorder. Both α-synuclein monomers are intrinsically disordered. The monomers nevertheless have 33% secondary structure. They are functional as long as mobile water molecules surround them. They realize every possible H-bonds with water. Oligomers are like globular proteins with 66% ordered structure. Amyloids are disordered to 75% and are poorly hydrated with loosely bound water. Their hydration is identical. Oligomers, amyloids have only half as much hydrating mobile water as monomers.

scholarly journals Protein–Protein Connections—Oligomer, Amyloid and Protein Complex—By Wide Line 1H NMR

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 757
Author(s):  
Mónika Bokor ◽  
Ágnes Tantos
Keyword(s):  
Protein Complex ◽  
Hydration Water ◽  
Thymosin Β4 ◽  
Wild Type ◽  
Protein Aggregate ◽  
Potential Barriers ◽  
Wide Line ◽  
Accessible Surface ◽  
Solvent Accessible Surface ◽  
Amyloid Oligomer

The amount of bonds between constituting parts of a protein aggregate were determined in wild type (WT) and A53T α-synuclein (αS) oligomers, amyloids and in the complex of thymosin-β4–cytoplasmic domain of stabilin-2 (Tβ4-stabilin CTD). A53T αS aggregates have more extensive βsheet contents reflected by constant regions at low potential barriers in difference (to monomers) melting diagrams (MDs). Energies of the intermolecular interactions and of secondary structures bonds, formed during polymerization, fall into the 5.41 kJ mol−1 ≤ Ea ≤ 5.77 kJ mol−1 range for αS aggregates. Monomers lose more mobile hydration water while forming amyloids than oligomers. Part of the strong mobile hydration water–protein bonds break off and these bonding sites of the protein form intermolecular bonds in the aggregates. The new bonds connect the constituting proteins into aggregates. Amyloid–oligomer difference MD showed an overall more homogeneous solvent accessible surface of A53T αS amyloids. From the comparison of the nominal sum of the MDs of the constituting proteins to the measured MD of the Tβ4-stabilin CTD complex, the number of intermolecular bonds connecting constituent proteins into complex is 20(1) H2O/complex. The energies of these bonds are in the 5.40(3) kJ mol−1 ≤ Ea ≤ 5.70(5) kJ mol−1 range.

scholarly journals Pairwise calculation of protein solvent-accessible surface areas

1998 ◽  
Vol 3 (4) ◽  
pp. 253-258 ◽  
Author(s):  
Arthur G. Street ◽  
Stephen L. Mayo
Keyword(s):  
Surface Areas ◽  
Accessible Surface ◽  
Solvent Accessible Surface

scholarly journals Dynamics and mechanism of ultrafast water–protein interactions

2016 ◽  
Vol 113 (30) ◽  
pp. 8424-8429 ◽  
Author(s):  
Yangzhong Qin ◽  
Lijuan Wang ◽  
Dongping Zhong
Keyword(s):  
Protein Interactions ◽  
Hydration Shell ◽  
Water Dynamics ◽  
Side Chain ◽  
Water Molecules ◽  
Ultrafast Dynamics ◽  
Hydration Water ◽  
Water Side ◽  
Dynamics And Function ◽  
And Function

Protein hydration is essential to its structure, dynamics, and function, but water–protein interactions have not been directly observed in real time at physiological temperature to our awareness. By using a tryptophan scan with femtosecond spectroscopy, we simultaneously measured the hydration water dynamics and protein side-chain motions with temperature dependence. We observed the heterogeneous hydration dynamics around the global protein surface with two types of coupled motions, collective water/side-chain reorientation in a few picoseconds and cooperative water/side-chain restructuring in tens of picoseconds. The ultrafast dynamics in hundreds of femtoseconds is from the outer-layer, bulk-type mobile water molecules in the hydration shell. We also found that the hydration water dynamics are always faster than protein side-chain relaxations but with the same energy barriers, indicating hydration shell fluctuations driving protein side-chain motions on the picosecond time scales and thus elucidating their ultimate relationship.

scholarly journals PAMAM dendrimer: a pH-controlled nanosponge

2017 ◽  
Vol 95 (9) ◽  
pp. 991-998 ◽  
Author(s):  
Prabal K. Maiti
Keyword(s):  
Accessible Surface Area ◽  
Pamam Dendrimer ◽  
Low Ph ◽  
Dynamics Simulation ◽  
Solvent Accessible Surface Area ◽  
Water Molecules ◽  
Accessible Volume ◽  
Accessible Surface ◽  
Solvent Accessible Surface ◽  
Ph Controlled

Using fully atomistic molecular dynamics simulation that are several hundred nanoseconds long, we demonstrate the pH-controlled sponge action of PAMAM dendrimer. We show how at varying pH levels, the PAMAM dendrimer acts as a wet sponge; at neutral or low pH levels, the dendrimer expands noticeably and the interior of the dendrimer opens up to host several hundreds to thousands of water molecules depending on the generation number. Increasing the pH (i.e., going from low pH to high pH) leads to the collapse of the dendrimer size, thereby expelling the inner water, which mimics the ‘sponge’ action. As the dendrimer size swells up at a neutral pH or low pH due to the electrostatic repulsion between the primary and tertiary amines that are protonated at this pH, there is dramatic increase in the available solvent accessible surface area (SASA), as well as solvent accessible volume (SAV).

scholarly journals Mutations in RBD of SARS-CoV-2 Omicron variant result stronger binding to human ACE2 protein

2021 ◽  
Author(s):  
Cecylia Severin Lupala ◽  
Yongjin Ye ◽  
Hong Chen ◽  
Xiaodong Su ◽  
Haiguang Liu
Keyword(s):  
Complex Structure ◽  
Tight Binding ◽  
Accessible Surface Area ◽  
Solvent Accessible Surface Area ◽  
Original Strain ◽  
Receptor Binding Domain ◽  
Bonding Interaction ◽  
Accessible Surface ◽  
Dynamics Simulations ◽  
Solvent Accessible Surface

The spreading of SARS-CoV-2 virus resulted the COVID-19 pandemic, which has caused more than 5 millions of death globally. Several major variants of SARS-CoV-2 have emerged and placed challenges in controlling the infections. The recently emerged Omicron variant raised serious concerns about reducing efficacy of antibodies or vaccines, due to its vast mutations. We modelled the complex structure of human ACE2 protein and the receptor binding domain of Omicron variant, then conducted atomistic molecular dynamics simulations to study the binding interactions. The analysis shows that the Omicron variant RBD binds more strongly to the human ACE2 protein than the original strain. The mutation at the ACE2-RBD interface enhanced the tight binding by increasing hydrogen bonding interaction and enlarging buried solvent accessible surface area.

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