Search results for "THERMODYNAMICS"
showing 10 items of 2774 documents
Investigation of protein folding by coarse-grained molecular dynamics with the UNRES force field.
2010
Coarse-grained molecular dynamics simulations offer a dramatic extension of the time-scale of simulations compared to all-atom approaches. In this article, we describe the use of the physics-based united-residue (UNRES) force field, developed in our laboratory, in protein-structure simulations. We demonstrate that this force field offers about a 4000-times extension of the simulation time scale; this feature arises both from averaging out the fast-moving degrees of freedom and reduction of the cost of energy and force calculations compared to all-atom approaches with explicit solvent. With massively parallel computers, microsecond folding simulation times of proteins containing about 1000 r…
Polar/Ionizable Residues in Transmembrane Segments: Effects on Helix-Helix Packing
2012
The vast majority of membrane proteins are anchored to biological membranes through hydrophobic alpha-helices. Sequence analysis of high-resolution membrane protein structures show that ionizable amino acid residues are present in transmembrane (TM) helices, often with a functional and/or structural role. Here, using as scaffold the hydrophobic TM domain of the model membrane protein glycophorin A (GpA), we address the consequences of replacing specific residues by ionizable amino acids on TM helix insertion and packing, both in detergent micelles and in biological membranes. Our findings demonstrate that ionizable residues are stably inserted in hydrophobic environments, and tolerated in t…
Investigation of Phosphorylation-Induced Folding of an Intrinsically Disordered Protein by Coarse-Grained Molecular Dynamics
2021
Apart from being the most common mechanism of regulating protein function and transmitting signals throughout the cell, phosphorylation has an ability to induce disorder-to-order transition in an intrinsically disordered protein. In particular, it was shown that folding of the intrinsically disordered protein, eIF4E-binding protein isoform 2 (4E-BP2), can be induced by multisite phosphorylation. Here, the principles that govern the folding of phosphorylated 4E-BP2 (pT37pT46 4E-BP2(18–62)) are investigated by analyzing canonical and replica exchange molecular dynamics trajectories, generated with the coarse-grained united-residue force field, in terms of local and global motions and the time…
Single tube optimisation of APOE genotyping based on melting curve analysis
2008
Objectives: To develop and validate a single-tube protocol for APOE genotyping using fluorescent probes. Design and methods: We have designed and validated a hybrid, single-tube, SimpleProbe/FRET probe protocol that takes advantage of the different probe wavelength emissions. Results: Our method offers high quality outcomes, minimum interferences between probe signals and is 100% concordant with the reference protocol. Conclusions: This method is cheaper, faster and more reliable and versatile than other alternatives proposed. © 2008 Elsevier Inc. All rights reserved.
Bohr-effect and buffering capacity of hemocyanin from the tarantula E. californicum.
2003
A previous report showed that binding of oxygen to the 24-meric hemocyanin from E. californicum does not correlate linearly with the release of protons as known from hemoglobin. However, this unusual complex phenomenological observation could not be explained at that time. Here, I present a full analysis of the thermodynamic coupling between protons and oxygen for the 24-meric tarantula hemocyanin in Ringer-solution based on the Nested-MWC-model. A strategy is presented which allows to reduce the number of free parameters when fitting the model to the data by including explicitly the equilibrium constants for binding of protons to the different conformations. The results show that the Neste…
Benchmark Study for the Cysteine-Histidine Proton Transfer Reaction in a Protein Environment: Gas Phase, COSMO, QM/MM Approaches.
2015
Proton transfer reactions are of crucial interest for the investigation of proteins. We have investigated the accuracy of commonly used quantum chemical methods for the description of proton transfer reactions in different environments (gas phase, COSMO, QM/MM) using the proton transfer between the catalytic dyad residues cysteine 145 and histidine 41 of SARS coronavirus main protease as a case study. The test includes thermodynamic, kinetic, and structural properties. The study comprises computationally demanding ab initio approaches (HF, CC2, MP2, SCS-CC2, SCS-MP2, CCSD(T)), popular density functional theories (BLYP, B3LYP, M06-2X), and semiempirical methods (MNDO/d, AM1, RM1, PM3, PM6). …
Surface Segregation Entropy of Protons and Oxygen Vacancies in BaZrO3
2016
The perovskite BaZrO3 has attracted considerable attention in the recent decade due to its high temperature proton conducting properties, and possible application as electrolyte in intermediate temperature fuel cells and electrolyzers. In this contribution, we performed, for the first time, first-principles calculations of the phonon contribution to the defect thermodynamics of the ZrO2 terminated (001) surface of BaZrO3. The approach allows us to determine both the segregation enthalpy and entropy of defects, which we apply to two fundamental defects in BaZrO3; fully charged oxygen vacancies (vO••) and protonic defects (OHO•). The calculations show that both defects exhibit favorable segre…
Charge-Neutral Constant pH Molecular Dynamics Simulations Using a Parsimonious Proton Buffer
2016
In constant pH molecular dynamics simulations, the protonation states of titratable sites can respond to changes of the pH and of their electrostatic environment. Consequently, the number of protons bound to the biomolecule, and therefore the overall charge of the system, fluctuates during the simulation. To avoid artifacts associated with a non-neutral simulation system, we introduce an approach to maintain neutrality of the simulation box in constant pH molecular dynamics simulations, while maintaining an accurate description of all protonation fluctuations. Specifically, we introduce a proton buffer that, like a buffer in experiment, can exchange protons with the biomolecule enabling its…
Theoretical study of the stabilization of cubic-phaseZrO2by impurities
1994
We have performed a thermodynamical analysis of the phase diagrams for ${\mathrm{ZrO}}_{2}$-CaO and ${\mathrm{ZrO}}_{2}$-MgO solid solutions which has demonstrated that differential heats of mixing are important parameters determining the stabilization of the cubic phase of ${\mathrm{ZrO}}_{2}$ by impurities. It is shown that the differential heats of mixing in the cubic phase of these systems should be lower than in the tetragonal phase. To understand this effect we have studied the electronic and geometrical structures of the pure and doped ${\mathrm{ZrO}}_{2}$ crystals. Three computational techniques were employed: the ab initio Hartree-Fock pseudopotential method is used to study the at…
Comparative bench study evaluation of different infant interfaces for non-invasive ventilation
2018
Abstract Background To compare, in terms of patient-ventilator interaction and performance, a new nasal mask (Respireo, AirLiquide, FR) with the Endotracheal tube (ET) and a commonly used nasal mask (FPM, Fisher and Paykel, NZ) for delivering Pressure Support Ventilation (PSV) in an infant model of Acute Respiratory Failure (ARF). Methods An active test lung (ASL 5000) connected to an infant mannequin through 3 different interfaces (Respireo, ET and FPM), was ventilated with a standard ICU ventilator set in PSV. The test lung was set to simulate a 5.5 kg infant with ARF, breathing at 50 and 60 breaths/min). Non-invasive ventilation (NIV) mode was not used and the leaks were nearly zero. Res…