scholarly journals Structural and thermodynamic analysis of factors governing the stability and thermal folding/unfolding of SazCA

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249866
Author(s):  
Shashi Kumar ◽  
Parag A. Deshpande
Keyword(s):  
Thermal Stability ◽  
Free Energy ◽  
Protein Stability ◽  
Explicit Knowledge ◽  
Fundamental Problem ◽  
Hydrophobic Surface ◽  
Amino Acid Residues ◽  
Different Temperatures ◽  
The Stability ◽  
Dynamics Simulations

Molecular basis of protein stability at different temperatures is a fundamental problem in protein science that is substantially far from being accurately and quantitatively solved as it requires an explicit knowledge of the temperature dependence of folding free energy of amino acid residues. In the present study, we attempted to gain insights into the thermodynamic stability of SazCA and its implications on protein folding/unfolding. We report molecular dynamics simulations of water solvated SazCA in a temperature range of 293-393 K to study the relationship between the thermostability and flexibility. Our structural analysis shows that the protein maintains the highest structural stability at 353 K and the protein conformations are highly flexible at temperatures above 353 K. Larger exposure of hydrophobic surface residues to the solvent medium for conformations beyond 353 K were identified from H-bond analysis. Higher number of secondary structure contents exhibited by SazCA at 353 K corroborated the conformations at 353 K to exhibit the highest thermal stability. The analysis of thermodynamics of protein stability revealed that the conformations that denature at higher melting temperatures tend to have greater maximum thermal stability. Our analysis shows that 353 K conformations have the highest melting temperature, which was found to be close to the experimental optimum temperature. The enhanced protein stability at 353 K due the least value of heat capacity at unfolding suggested an increase in folding. Comparative Gibbs free energy analysis and funnel shaped energy landscape confirmed a transition in folding/unfolding pathway of SazCA at 353 K.

scholarly journals Study of the stability and unfolding mechanism of BBA1 by molecular dynamics simulations at different temperatures

1999 ◽  
Vol 8 (6) ◽  
pp. 1292-1304 ◽  
Author(s):  
Lu Wang ◽  
Yong Duan ◽  
Rebecca Shortle ◽  
Barbara Imperiali ◽  
Peter A. Kollman
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Different Temperatures ◽  
The Stability ◽  
Dynamics Simulations

scholarly journals Understanding the essential proton-pumping kinetic gates and decoupling mutations in cytochrome c oxidase

2017 ◽  
Vol 114 (23) ◽  
pp. 5924-5929 ◽  
Author(s):  
Ruibin Liang ◽  
Jessica M. J. Swanson ◽  
Mårten Wikström ◽  
Gregory A. Voth
Keyword(s):  
Free Energy ◽  
Molecular Mechanisms ◽  
Proton Pumping ◽  
Amino Acid Residues ◽  
Reactive Molecular Dynamics ◽  
Chemical Catalysis ◽  
Energy Profiles ◽  
High Proton ◽  
Pumping Efficiency ◽  
Dynamics Simulations

Cytochrome c oxidase (CcO) catalyzes the reduction of oxygen to water and uses the released free energy to pump protons against the transmembrane proton gradient. To better understand the proton-pumping mechanism of the wild-type (WT) CcO, much attention has been given to the mutation of amino acid residues along the proton translocating D-channel that impair, and sometimes decouple, proton pumping from the chemical catalysis. Although their influence has been clearly demonstrated experimentally, the underlying molecular mechanisms of these mutants remain unknown. In this work, we report multiscale reactive molecular dynamics simulations that characterize the free-energy profiles of explicit proton transport through several important D-channel mutants. Our results elucidate the mechanisms by which proton pumping is impaired, thus revealing key kinetic gating features in CcO. In the N139T and N139C mutants, proton back leakage through the D-channel is kinetically favored over proton pumping due to the loss of a kinetic gate in the N139 region. In the N139L mutant, the bulky L139 side chain inhibits timely reprotonation of E286 through the D-channel, which impairs both proton pumping and the chemical reaction. In the S200V/S201V double mutant, the proton affinity of E286 is increased, which slows down both proton pumping and the chemical catalysis. This work thus not only provides insight into the decoupling mechanisms of CcO mutants, but also explains how kinetic gating in the D-channel is imperative to achieving high proton-pumping efficiency in the WT CcO.

scholarly journals Molecular Investigation of Chicken Acid-Sensing Ion Channel 1 β11-12 Linker Isomerization and Channel Kinetics

2021 ◽  
Vol 15 ◽  
Author(s):  
Matthew L. Rook ◽  
Anna Ananchenko ◽  
Maria Musgaard ◽  
David M. MacLean
Keyword(s):  
Molecular Dynamics ◽  
Ion Channel ◽  
Molecular Dynamics Simulations ◽  
Time Window ◽  
Amino Acid Residues ◽  
Channel Kinetics ◽  
Physiological Importance ◽  
Recovery Processes ◽  
The Stability ◽  
Dynamics Simulations

Structures of the trimeric acid-sensing ion channel have been solved in the resting, toxin-bound open and desensitized states. Within the extracellular domain, there is little difference between the toxin-bound open state and the desensitized state. The main exception is that a loop connecting the 11th and 12th β-strand, just two amino acid residues long, undergoes a significant and functionally critical re-orientation or flipping between the open and desensitized conformations. Here we investigate how specific interactions within the surrounding area influence linker stability in the “flipped” desensitized state using all-atom molecular dynamics simulations. An inherent challenge is bringing the relatively slow channel desensitization and recovery processes (in the milliseconds to seconds) within the time window of all-atom simulations (hundreds of nanoseconds). To accelerate channel behavior, we first identified the channel mutations at either the Leu414 or Asn415 position with the fastest recovery kinetics followed by molecular dynamics simulations of these mutants in a deprotonated state, accelerating recovery. By mutating one residue in the loop and examining the evolution of interactions in the neighbor, we identified a novel electrostatic interaction and validated prior important interactions. Subsequent functional analysis corroborates these findings, shedding light on the molecular factors controlling proton-mediated transitions between functional states of the channel. Together, these data suggest that the flipped loop in the desensitized state is stabilized by interactions from surrounding regions keeping both L414 and N415 in place. Interestingly, very few mutations in the loop allow for equivalent channel kinetics and desensitized state stability. The high degree of sequence conservation in this region therefore indicates that the stability of the ASIC desensitized state is under strong selective pressure and underlines the physiological importance of desensitization.

scholarly journals Thermodynamic Analysis and Calculations of (Fe-Co) Alloy by Modeling and Simulation using Thermo-Calc Software

2018 ◽  
pp. 120-123
Author(s):  
Syed Mahmood Shah ◽  
Nasib Ullah ◽  
Bakhtar Ullah ◽  
Muhammad Shehzad Khan ◽  
Tariq Usman
Keyword(s):  
Phase Diagram ◽  
Free Energy ◽  
Gibbs Free Energy ◽  
Calphad Method ◽  
Negative Deviation ◽  
Activity Curve ◽  
Thermo Calc Software ◽  
Different Temperatures ◽  
The Stability ◽  
Co Alloys

In this paper Thermodynamic calculation is shown. We have found simulation for phase diagram, Gibbs free energy and Activity curve at different temperatures (1200 K, 1225 K and 1250 K). Phase diagrams, Gibbs free-energy and the component activities of (Fe-Co) alloys system were calculated by Calphad method. Results show that the values of Gibbs energy were negative, which shows the stability of (Fe-Co). Negative deviation had occurred from Raoult’s Law in activities, which indicates that there is strong interaction between Fe and Co in (Fe-Co) alloy. By increasing the temperature the activity increases and deviation in activity decreases. For all the thermodynamic calculations the Thermo-Calc software, databases and Calphad method have used.

scholarly journals A Comparative Study to Decipher the Structural and Dynamics Determinants Underlying the Activity and Thermal Stability of GH-11 Xylanases

2021 ◽  
Vol 22 (11) ◽  
pp. 5961
Author(s):  
Jelena Vucinic ◽  
Gleb Novikov ◽  
Cédric Y. Montanier ◽  
Claire Dumon ◽  
Thomas Schiex ◽  
...  
Keyword(s):  
Thermal Stability ◽  
Md Simulations ◽  
Structural Basis ◽  
Depth Analysis ◽  
Molecular Determinants ◽  
Binding Cleft ◽  
The Stability ◽  
Dynamics Simulations ◽  
Thermal Stability Of ◽  
The Ideal

With the growing need for renewable sources of energy, the interest for enzymes capable of biomass degradation has been increasing. In this paper, we consider two different xylanases from the GH-11 family: the particularly active GH-11 xylanase from Neocallimastix patriciarum, NpXyn11A, and the hyper-thermostable mutant of the environmentally isolated GH-11 xylanase, EvXyn11TS. Our aim is to identify the molecular determinants underlying the enhanced capacities of these two enzymes to ultimately graft the abilities of one on the other. Molecular dynamics simulations of the respective free-enzymes and enzyme–xylohexaose complexes were carried out at temperatures of 300, 340, and 500 K. An in-depth analysis of these MD simulations showed how differences in dynamics influence the activity and stability of these two enzymes and allowed us to study and understand in greater depth the molecular and structural basis of these two systems. In light of the results presented in this paper, the thumb region and the larger substrate binding cleft of NpXyn11A seem to play a major role on the activity of this enzyme. Its lower thermal stability may instead be caused by the higher flexibility of certain regions located further from the active site. Regions such as the N-ter, the loops located in the fingers region, the palm loop, and the helix loop seem to be less stable than in the hyper-thermostable EvXyn11TS. By identifying molecular regions that are critical for the stability of these enzymes, this study allowed us to identify promising targets for engineering GH-11 xylanases. Eventually, we identify NpXyn11A as the ideal host for grafting the thermostabilizing traits of EvXyn11TS.

scholarly journals Thermodynamic Analysis and Calculations of (Fe-Co) Alloy by Modeling and Simulation using Thermo-Calc Software

2018 ◽  
pp. 35-38
Author(s):  
Syed Mahmood Shah ◽  
Nasib Ullah ◽  
Bakhtar Ullah ◽  
Muhammad Shehzad Khan ◽  
Tariq Usman
Keyword(s):  
Phase Diagram ◽  
Free Energy ◽  
Gibbs Free Energy ◽  
Calphad Method ◽  
Negative Deviation ◽  
Activity Curve ◽  
Thermo Calc Software ◽  
Different Temperatures ◽  
The Stability ◽  
Co Alloys

In this paper Thermodynamic calculation is shown. We have found simulation for phase diagram, Gibbs free energy and Activity curve at different temperatures (1200 K, 1225 K and 1250 K). Phase diagrams, Gibbs free-energy and the component activities of (Fe-Co) alloys system were calculated by Calphad method. Results show that the values of Gibbs energy were negative, which shows the stability of (Fe-Co). Negative deviation had occurred from Raoult’s Law in activities, which indicates that there is strong interaction between Fe and Co in (Fe-Co) alloy. By increasing the temperature the activity increases and deviation in activity decreases. For all the thermodynamic calculations the Thermo-Calc software, databases and Calphad method have used.

scholarly journals THERMAL STABILITY OF SYNTHETIC PEPTIDES MIMICKING THE SEQUENCE OF THE REGION CONTAINING THE SKIP RESIDUES IN SQUID MYOSIN ROD

2017 ◽  
Vol 20 (2) ◽  
pp. 319
Author(s):  
Yoshihiro Ochiai ◽  
Mala Nurilmala ◽  
GuoFeng Wang ◽  
Shugo Watabed
Keyword(s):  
Thermal Stability ◽  
Synthetic Peptides ◽  
Coiled Coil ◽  
Thick Filament ◽  
Heptad Repeat ◽  
Major Protein ◽  
Amino Acid Residues ◽  
The Stability ◽  
Fish And Shellfish ◽  
Myosin Rod

Myosin is the major protein in skeletal muscles including those of fish and shellfish. The characteristics of this protein are closely related to the biological function and the quality and physical properties of muscle<br />food. In the myosin rod (the coiled-coil region of myosin), several amino acid residues, known as skip residues, seem to destabilize the ordered structure (heptad repeat). These residues might be responsible for reducing thermal stability. Attempts were thus made to examine the role of these residues in the rod of squid myosin, based on the thermodynamic properties of synthetic peptides which have been designed to mimic the partial sequence of myosin heavy chain from the squid Todarodes pacificus mantle muscle. Five peptides, namely, with the sequence of Trp1343 -Ala1372  having the skip residue Glu1357 at the center (Peptide WT), without the skip residue (Peptide Δ), with the replacements of the skip residue (Glu) by Ile, Gln and Pro (Peptides E/I, E/Q, and E/P, respectively) to modify the helix forming propensity, were synthesized. The results obtained showed that the stability of the peptides as measured by circular dichroism spectrometry was in the order of Peptide Δ &gt; Peptide WT &gt; Peptide E/Q &gt; Peptide E/P &gt; Peptide E/I. It is suggested that the presence of the skip residues dexterously tunes the stability or flexibility of the coiled-coil structure, thus possibly regulating thick filament formation and further gel formation ability of myosin.

scholarly journals On the perfect diameter condition to optimize the antibiotic nanoencapsulation: case of gramicidin

2019 ◽  
Vol 8 (3) ◽  
pp. 654-660 ◽  
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Ionic Transport ◽  
Transport Mechanisms ◽  
Ion Diffusion ◽  
Energy Profiles ◽  
The Stability ◽  
Dynamics Simulations ◽  
Antibiotic Structure ◽  
Free Energy Profiles

In the present work, we propose to investigate the ionic transport mechanisms in a new optimized biomimetic system. Our studies performed using classical molecular dynamics simulations show that it was possible to optimize the geometry of a hydrophobic nanopore in order to stabilize a small antibiotic by confinement. The analyses of the antibiotic structure gathered with the free energy profiles of ion diffusion through the channel of the antibiotic demonstrate the stability and the functional encapsulation of the drug. It opens a new way to build biomimetic nanochannel or nanovector for drug delivery.

scholarly journals The stability of the coiled-coil structure near to N-terminus influence the heat resistance of harpin proteins from Xanthomonas

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yue Liu ◽  
Xiaoyun Zhou ◽  
Wenbo Liu ◽  
Weiguo Miao
Keyword(s):  
Thermal Stability ◽  
Heat Resistance ◽  
Coiled Coil ◽  
Temperature Treatment ◽  
High Temperature Treatment ◽  
Amino Acid Residues ◽  
Important Amino Acid ◽  
C Terminus ◽  
N Terminus ◽  
The Stability

Abstract Background Heat resistance is a common characteristic of harpins, a class of proteins found in Gram-negative bacteria, which may be related to the stability of coiled-coil (CC) structure. The CC structure is a ubiquitous protein folding and assembly motif made of α-helices wrapping around each other forming a supercoil. Specifically, whether the stability of the CC structure near to N-terminus of four selected harpin proteins from Xanthomonas (hereafter referred to as Hpa1) would influence their characteristics of heat resistance was investigated. We used bioinformatics approach to predict the structure of Hpa1, used the performance of hypersensitive response (HR)-induction activity of Hpa1 and circular dichroism (CD) spectral analyses to detect the relationship between the stability of the CC structure of Hpa1 and heat resistance. Results Each of four-selected Hpa1 has two α-helical regions with one in their N-terminus that could form CC structure, and the other in their C-terminus that could not. And the important amino acid residues involved in the CC motifs are located on helices present on the surface of these proteins, indicating they may engage in the formation of oligo mericaggregates, which may be responsible for HR elicitation by harpins and their high thermal stability. Increased or decreased the probability of forming a CC could either induce a stronger HR response or eliminate the ability to induce HR in tobacco after high temperature treatment. In addition, although the four Hpa1 mutants had little effect on the induction of HR by Hpa1, its thermal stability was significantly decreased. The α-helical content increased with increasing temperature, and the secondary structures of Hpa1 became almost entirely α-helices when the temperature reached 200 °C. Moreover, the stability of the CC structure near to N-terminus was found to be positively correlated with the heat resistance of Hpa1. Conclusions The stability of the CC structure might sever as an inner drive for mediating the heat resistance of harpin proteins. Our results offer a new insight into the interpretation of the mechanism involved in the heat resistance of harpin protein and provide a theoretical basis for further harpin function investigations and structure modifications.

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