New simulation insights on the structural transition mechanism of bovine rhodopsin activation.

Inactive rhodopsin can absorb photons, which induces different structural transitions that finally activate rhodopsin. We have examined the change in spatial configurations and physicochemical factors that result during the transition mechanism from the inactive to the active rhodopsin state via intermediates. During the activation process, many existing atomic contacts are disrupted, and new ones are formed. This is related to the movement of Helix 5, which tilts away from Helix 3 in the intermediate state in lumirhodopsin and moves closer to Helix 3 again in the active state. Similar patterns of changing atomic contacts are observed between Helices 3 and 5 of the adenosine and neurotensin receptors. In addition, residues 220-238 of rhodopsin, which are disordered in the inactive state, fold in the active state before binding to the Gα, where it catalyzes GDP/GTP exchange on the Gα subunit. Finally, molecular dynamics simulations in the membrane environment revealed that the arrestin binding region adopts a more flexible extended conformation upon phosphorylation, likely promoting arrestin binding and inactivation. In summary, our results provide additional structural understanding of specific rhodopsin activation which might be relevant to other Class A G protein-coupled receptor proteins.

Statistical and molecular dynamics (MD) simulation approach to investigate the role of intrinsically disordered regions of shikimate dehydrogenase in microorganisms surviving at different temperatures.

Hyperthermophiles, a subset of prokaryotes that thrive in adverse temperatures, potentially utilize the protein molecular biosystem for maintaining thermostability in a wide range of temperatures. Recent studies revealed that these organisms have smaller proportions of intrinsically disordered proteins. In this study, we performed sequence and structural analysis to investigate the maintenance of protein conformation and their stability at different temperatures. The sequence analysis reveals the higher proportion of charged amino acids are responsible for preventing the helix formation and, hence, become disordered regions. For structural analysis, we chose shikimate dehydrogenase from four species, namely Listeria monocytogenes, Escherichia coli, Thermus thermophilus, and Methanopyrus kandleri, and evaluated the protein adaptation at 283 K, 300 K, and 395 K temperatures. From this investigation, we found more residues of shikimate dehydrogenase prefer an order-to-disorder transition at 395 K only for hyperthermophilic species. The solvent-accessible surface area (SASA) and hydrogen-bond analysis revealed that the tertiary conformation and the number of hydrogen bonds for hyperthermophilic shikimate dehydrogenase are highly preserved at 395 K, compared to 300 K. Our simulation results conjointly provide shikimate dehydrogenase of hyperthermophile which resists high temperatures through stronger protein tertiary conformations.

Titanium dioxide nanoparticle-protein interaction explained by docking approach.

Titanium dioxide has been proven for toxicity by in vitro and in vivo approaches, however, further studies are needed in nano-toxicological research using in silico analysis. In this study, Autodock 4.0.5 was used in an attempt to evaluate the interaction of titanium dioxide with proteins. Different cellular proteins were sorted to study the interaction, binding sites, and active sites as a pocket. These pockets have been determined using CastP - an online server. The analysis for the docked structures was performed with regard to the most efficient binding with amino acids. This study is the first of its kind to report on the in silico docking interaction of titanium dioxide nanoparticles without any surface modification. The higher negative binding energy shows strong binding of titanium dioxide with proteins. A strong interaction with different cellular proteins was observed, and more specifically, titanium dioxide nanoparticles showed frequent interaction with proline, lysine, as well as leusine.