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The time-dependent relaxation of a dynamical system may exhibit a power-law behavior that is superimposed by log-periodic oscillations. D. Sornette [Phys. Rep. 297, 239 (1998)] showed that this behavior can be explained by a discrete scale invariance of the system, which is associated with discrete and equidistant timescales on a logarithmic scale. Examples include such diverse fields as financial crashes, random diffusion, and quantum topological materials. Recent time-resolved experiments and molecular dynamics simulations suggest that discrete scale invariance may also apply to hierarchical dynamics in proteins, where several fast local conformational changes are a prerequisite for a slow global transition to occur. Employing entropy-based timescale analysis and Markov state modeling to a simple one-dimensional hierarchical model and biomolecular simulation data, it is found that hierarchical systems quite generally give rise to logarithmically spaced discrete timescales. By introducing a one-dimensional reaction coordinate that collectively accounts for the hierarchically coupled degrees of freedom, the free energy landscape exhibits a characteristic staircase shape with two metastable end states, which causes the log-periodic time evolution of the system. The period of the log-oscillations reflects the effective roughness of the energy landscape and can, in simple cases, be interpreted in terms of the barriers of the staircase landscape. [ABSTRACT FROM AUTHOR]

Recent time-resolved experiments and accompanying molecular dynamics simulations allow us to monitor the flow of vibrational energy in biomolecules. As a simple means to describe these experimental and simulated data, Buchenberg et al. [J. Phys. Chem. Lett. 7, 25 (2016)] suggested a master equation model that accounts for the energy transport from an initially excited residue to some target residue. The transfer rates of the model were obtained from two scaling rules, which account for the energy transport through the backbone and via tertiary contacts, respectively, and were parameterized using simulation data of a small α-helical protein at low temperatures. To extend the applicability of the model to general proteins at room temperature, here a new parameterization is presented, which is based on extensive nonequilibrium molecular dynamics simulations of a number of model systems. With typical transfer times of 0.5–1 ps between adjacent residues, backbone transport represents the fastest channel of energy flow. It is well described by a diffusive-type scaling rule, which requires only an overall backbone diffusion coefficient and interatom distances as input. Contact transport, e.g., via hydrogen bonds, is considerably slower (6–30 ps) at room temperature. A new scaling rule depending on the inverse square contact distance is suggested, which is shown to successfully describe the energy transport in the allosteric protein PDZ3. Since both scaling rules require only the structure of the considered system, the model provides a simple and general means to predict energy transport in proteins. To identify the pathways of energy transport, Monte Carlo Markov chain simulations are performed, which highlight the competition between backbone and contact transport channels. [ABSTRACT FROM AUTHOR]

Conventional drug delivery systems suffer from poor absorption and poor bioavailability at the target site due to either very weak or very strong adsorption of drug on the carrier. Porous 2D nanostructures can offer better drug delivery system provided the system chosen has suitable cavity with heteroatoms for reasonable interaction with drug molecules. C2N is a surface of choice in this regard; therefore, potential of C2N surface as drug delivery system for nitrosourea and fluorouracil (drugs) is explored here. Both nitrosourea and fluorouracil interacted with the electron rich central cavity of C2N. Different structural and electronic parameters show that both drugs have good adsorption on C2N surface and thus can be carried to the target easily. Values of interaction and basis set superposition error (BSSE) corrected energies are slightly higher for nitrosourea@C2N as compared to fluorouracil@C2N. While all other properties such as non-covalent interaction (NCI), symmetry-adapted perturbation theory (SAPT0), quantum theory of atoms in molecules (QTAIM), natural bond orbital (NBO), electron density difference (EDD) and frontier molecular orbital (FMO) analyses illustrate that C2N is better carrier for nitrosourea than fluorouracil. The off-loading of drug is explored through molecular dynamics simulations which reveal that slightly elevated temperature can cause off-loading of the drug at the target cancer cell, which usually have temperature higher than the normal cells. MD simulations reveal that atomic interactions between the drugs and C2N are destabilized at higher temperatures. Comparison of the loading and off-loading mechanism with other surfaces reported in the literature reveal that C2N is a better carrier for these drugs. [ABSTRACT FROM AUTHOR]

GabR from Bacillus subtilis is a transcriptional regulator belonging to the MocR subfamily of the GntR regulators. The structure of the MocR regulators is characterized by the presence of two domains: i) a N-terminal domain, about 60 residue long, possessing the winged-Helix-Turn-Helix (wHTH) architecture with DNA recognition and binding capability; ii) a C-terminal domain (about 350 residue) folded as the pyridoxal 5’-phosphate (PLP) dependent aspartate aminotransferase (AAT) with dimerization and effector binding functions. The two domains are linked to each other by a peptide bridge. Although structural and functional characterization of MocRs is proceeding at a fast pace, virtually nothing is know about the molecular changes induced by the effector binding and on how these modifications influence the properties of the regulator. An extensive molecular dynamics simulation on the crystallographic structure of the homodimeric B. subtilis GabR has been undertaken with the aim to envisage the role and the importance of conformational flexibility in the action of GabR. Molecular dynamics has been calculated for the apo (without PLP) and holo (with PLP bound) forms of the GabR. A comparison between the molecular dynamics trajectories calculated for the two GabR forms suggested that one of the wHTH domain detaches from the AAT-like domain in the GabR PLP-bound form. The most evident conformational change in the holo PLP-bound form is represented by the rotation and the subsequent detachment from the subunit surface of one of the wHTH domains. The movement is mediated by a rearrangement of the linker connecting the AAT domain possibly triggered by the presence of the negative charge of the PLP cofactor. This is the second most significant conformational modification. The C-terminal section of the linker docks into the “active site” pocket and establish stabilizing contacts consisting of hydrogen-bonds, salt-bridges and hydrophobic interactions. [ABSTRACT FROM AUTHOR]

Background: Pandemics greatly affected human health due to changes in dietary habits and lifestyle., Methods: A multi-centric comparative cross-sectional study was conducted online using a structured questionnaire with 323 respondents from two medical colleges of Lahore, Pakistan. The collected data was analyzed including various variables of dietary habits, lifestyle changes and were compared by using paired sample t-test. Chi-square test was applied to measure the relation of weight gain with lifestyle and dietary habits changes., Result: Out of 323 participants, 64.5% of them observed an increase in their weights and 64.1% of respondents noticed an increase in caloric intake. An increase in chicken, milk, oil, sugar and legumes intake was increased significantly during the quarantine. The lifestyle changes were noted in 91.6% of participants and decreased physical activity, working duration and outdoor games were found significant. Out of 7.4% of students who were smokers, 6.8% of them quit smoking during the quarantine., Conclusion: A significant increase in weight is indicated during quarantine as compared to before quarantine probably due to the changes in dietary habits and lifestyle. If the pandemic prolongs, the problem of weight gain may worsen and lead to obesity and other health problems., Competing Interests: Conflict of interest The authors state that there is no conflict of interest., (© 2023 Greater Baltimore Medical Center.)

Background Since the first case of coronavirus disease-19 (COVID-19) in Pakistan was reported in February 2020, the medical and paramedical staff has been working on the frontlines to deal with this disease. They have been facing significant strain and stress due to the pandemic, affecting their social, mental, and personal life. The purpose of this study is to investigate the psychological effects of the COVID-19 pandemic, etiology, personal coping mechanisms, and the strategies that are being adopted to reduce stress by the healthcare workers (HCWs) working in COVID-19 dedicated wards (group 2) and compare it with staff working in other departments but not in COVID-19 wards amid this pandemic (group 1) in various hospitals of Lahore, Pakistan. Methods The comparative cross-sectional study was designed which included doctors, nurses, and allied health professionals from various hospitals of Lahore, Pakistan. A questionnaire was designed which consisted of five sections, and 51 questions. A Chi-square test was used to compare the responses between these two groups. Results The study questionnaire was submitted by 200 participants, 100 responses for each group (see the Appendix). In group 1, HCWs not working in COVID-19 dedicated floors were afraid of getting infected, transmitting the infection to their families and concerned about using personal protective equipment (PPE) improperly. They reported a lack of concentration and tense muscles. The coping mechanisms of this group were exercise, strict precautions at work, and social distancing measures. While HCWs serving in COVID-19 dedicated wards were concerned and afraid of putting their families at risk by working in the high-risk environment; the major stresses in this group were: lack of knowledge about proper strategies for treatment, they faced insecurity due to physical and verbal violence by caretakers of COVID-19 patients, and lack of concentration. The coping mechanism was the support of their families and taking strict precautions, with self-isolation if required, to avoid any disease transmission to their families. The proposed strategies to be implemented included teaching skills for self-rescue as well as the implementation of policies at the administrative level to reduce working hours and frequent shift rotation. Conclusion The COVID-19 outbreak posed a great deal of mental stress among HCWs working on the COVID-19 floor as well as those serving in other departments of the hospital. The HCWs from group 1 were most afraid of getting infected and putting family members at risk, experienced tense muscles and lack of concentration, coped their stress by exercise and being more vigilant, and suggested the strategies of teaching skills for self-rescue and better community awareness. While the staff from the second group were most afraid of being the source of infection and violence from the caretakers of patients, experienced tense muscles, used family support, and strict isolation measures as coping mechanisms and suggested the strategies of self-rescue and increase in wages of directly exposed healthcare workers to deal with such pandemics in future in a better way., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2020, Shahid et al.)

We explore the capability of the non-natural amino acid azidohomoalanine (AHA) as an IR label to sense relatively small structural changes in proteins with the help of 2D IR difference spectroscopy. To that end, we AHA-labeled an allosteric protein (the PDZ2 domain from human tyrosine-phosphatase 1E) and furthermore covalently linked it to an azobenzene-derived photoswitch as to mimic its conformational transition upon ligand binding. To determine the strengths and limitations of the AHA label, in total six mutants have been investigated with the label at sites with varying properties. Only one mutant revealed a measurable 2D IR difference signal. In contrast to the commonly observed frequency shifts that report on the degree of solvation, in this case we observe an intensity change. To understand this spectral response, we performed classical MD simulations, evaluating local contacts of the AHA labels to water molecules and protein side chains and calculating the vibrational frequency on the basis of an electrostatic model. Although these simulations revealed in part significant and complex changes of the number of intraprotein and water contacts upon trans-cis photoisomerization, they could not provide a clear explanation of why this one label would stick out. Subsequent quantum-chemistry calculations suggest that the response is the result of an electronic interaction involving charge transfer of the azido group with sulfonate groups from the photoswitch. To the best of our knowledge, such an effect has not been described before.