0000000000812930
AUTHOR
Serena Donnini
Protonation of the Biliverdin IXα Chromophore in the Red and Far-Red Photoactive States of a Bacteriophytochrome
The tetrapyrrole chromophore biliverdin IXα (BV) in the bacteriophytochrome from Deinococcus radiodurans (DrBphP) is usually assumed to be fully protonated, but this assumption has not been systematically validated by experiments or extensive computations. Here, we use force field molecular dynamics simulations and quantum mechanics/molecular mechanics calculations with density functional theory and XMCQDPT2 methods to investigate the effect of the five most probable protonation forms of BV on structural stability, binding pocket interactions, and absorption spectra in the two photochromic states of DrBphP. While agreement with X-ray structural data and measured UV/vis spectra suggest that …
Charge-Neutral Constant pH Molecular Dynamics Simulations Using a Parsimonious Proton Buffer
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…
Protonation of the Biliverdin IXα Chromophore in the Red and Far-Red Photoactive States of Bacteriophytochrome
The tetrapyrrole chromophore biliverdin IXα (BV) in the bacteriophytochrome from Deinococcus radiodurans (DrBphP) is usually assumed to be fully protonated, but this assumption has not been systematically validated by experiments or extensive computations. Here, we use force field molecular dynamics simulations and quantum mechanics/molecular mechanics calculations with density functional theory and XMCQDPT2 methods to investigate the effect of the five most probable protonation forms of BV on structural stability, binding pocket interactions, and absorption spectra in the two photochromic states of DrBphP. While agreement with X-ray structural data and measured UV/vis spectra suggest that …
Acid–Base Properties and Surface Charge Distribution of the Water-Soluble Au102(pMBA)44 Nanocluster
The pKa of the p-mercaptobenzoic acid (pMBA) ligands in the Au102(pMBA)44 nanocluster was measured by using acid–base and IR titration. The observed macroscopic pKa = 6.18 ± 0.05 is significantly more basic than that of free pMBA (pKa = 4.16), and the protonation behavior is anticooperative according to the Hill coefficient n = 0.64 ± 0.04. The cluster is truly water-soluble when more than 22 and insoluble when fewer than 7 ligands are in the deprotonated state. In order to obtain more insight into the anticooperative character, the cluster was modeled at pH ∼6.2 using constant pH molecular dynamics simulations. The pKa values of the individual pMBAs are in the range of 5.18–7.58, depending…
Understanding and Controlling Food Protein Structure and Function in Foods: Perspectives from Experiments and Computer Simulations
The structure and interactions of proteins play a critical role in determining the quality attributes of many foods, beverages, and pharmaceutical products. Incorporating a multiscale understanding of the structure–function relationships of proteins can provide greater insight into, and control of, the relevant processes at play. Combining data from experimental measurements, human sensory panels, and computer simulations through machine learning allows the construction of statistical models relating nanoscale properties of proteins to the physicochemical properties, physiological outcomes, and tastes of foods. This review highlights several examples of advanced computer simulations at mol…
Chromophore-Protein Interplay During the Phytochrome Photocycle Revealed by Step-Scan FTIR Spectroscopy
Phytochrome proteins regulate many photoresponses of plants and microorganisms. Light absorption causes isomerization of the biliverdin chromophore, which triggers a series of structural changes to activate the signaling domains of the protein. However, the structural changes are elusive, and therefore the molecular mechanism of signal transduction remains poorly understood. Here, we apply two-color step-scan infrared spectroscopy to the bacteriophytochrome from Deinococcus radiodurans. We show by recordings in H2O and D2O that the hydrogen bonds to the biliverdin D-ring carbonyl become disordered in the first intermediate (Lumi-R) forming a dynamic microenvironment, then completely detach …
Tracking Changes in Protonation and Conformation during Photoactivation of a Phytochrome Protein
Phytochromes are photosensor proteins in plants and bacteria. The biological response is mediated by structural changes that follow photon absorption in the protein complex. The initial step is the photoisomerization of the biliverdin chromophore. How this leads to large-scale structural changes of the whole complex is, however, poorly understood. In this work, we use molecular dynamics (MD) simulations to investigate the structural changes after isomerization. In particular, we perform MD simulations at constant pH, using a recently developed method, to explore the effect of chromophore isomerization on the protonation (pKa) of nearby residues. In addition, we use a hybrid quantum mechanic…
Fatty Acid Aggregates Simulated using Constant pH Molecular Dynamics with a Coarse-Grained Model
Fatty acids are crucial biomolecules, important for lipid metabolism, signaling, models for protocell membranes, soaps, industrial applications, and drug delivery. Oleic acid has complex phase behavior with respect to the protonation state of the carboxylic head group, which depends on the pH of the solution. Oils form at low pHs, vesicles at intermediate pHs, and micelles at high pHs. We use constant pH molecular dynamics with the MARTINI coarse-grained model to investigate oleic acid aggregates at different pH conditions. We determine titration curves for the oleic acid monomers in different aggregates, and observe a shift in the microscopic pKa. In agreement with experimental results, th…