Highlights A survey is conducted of different age groups from various educational institutes in Delhi - National Capital Region (NCR), India. The impact of COVID -19 on the students of different age groups: time spent on online classes and self-study, medium used for learning, sleeping habits, daily fitness routine, and the subsequent effects on weight, social life, and mental health. It is observed that in order to deal with stress and anxiety, participants adopted different coping mechanisms and also sought help from their near ones. It is also reported that the student’s engagement on social media platforms among different age categories. This study suggests that public authorities should take all the necessary measures to enhance the learning experience by mitigating the negative impacts caused due to the COVID -19 outbreak. It is investigated and analysed the potential consequences of the COVID-19 pandemic on the life of students. Our research shows that there is a wide gap between the government's policy aspirations and the implementation of these online education policies at the grassroots level. Moreover, our study attempts to assess the mental situation of students of different age groups using different parameters including sleeping habits, daily fitness routine, and social support. Further, we analyse different coping mechanisms used by students to deal with the current situation.

Calculating the absolute binding free energies is a challenging task. Reliable estimates of binding free energies should provide a guide for rational drug design. It should also provide us with deeper understanding of the correlation between protein structure and its function. Further applications may include identifying novel molecular scaffolds and optimizing lead compounds in computeraided drug design. Available options to evaluate the absolute binding free energies range from the rigorous but expensive free energy perturbation to the microscopic Linear Response Approximation (LRA/β version) and its variants including the Linear Interaction Energy (LIE) to the more approximated and considerably faster scaled Protein Dipoles Langevin Dipoles (PDLD/ S-LRA version), as well as the less rigorous Molecular Mechanics Poisson-Boltzmann/Surface Area (MM/PBSA) and Generalized Born/Surface Area (MM/GBSA) to the less accurate scoring functions. There is a need for an assessment of the performance of different approaches in terms of computer time and reliability. We present a comparative study of the LRA/β, the LIE, the PDLD/ S-LRA/β and the more widely used MM/PBSA and assess their abilities to estimate the absolute binding energies. The LRA and LIE methods perform reasonably well but require specialized parameterization for the non-electrostatic term. On the average, the PDLD/S-LRA/β performs effectively. Our assessment of the MM/PBSA is less optimistic. This approach appears to provide erroneous estimates of the absolute binding energies due to its incorrect entropies and the problematic treatment of electrostatic energies. Overall, the PDLD/S-LRA/β appears to offer an appealing option for the final stages of massive screening approaches.

The process of ligand binding is very complex due to the intricacy of the interrelated processes that are difficult to predict and quantify. One of the most important requirements in computer-aided drug design is the ability to reliably evaluate the binding free energies. However, deeper understanding of the origin of the observed binding free energies requires the ability to decompose these free energies to their contributions from different interactions. Furthermore, it is important to evaluate the relative entropic and enthalpic contributions to the overall free energy. Such an evaluation is useful for assessing temperature effects and exploring specialized options in enzyme design. Unfortunately, calculations of binding entropies have been much more challenging than calculations of binding free energies. This work is probably the first to present microscopic evaluation of all of the relevant components to the binding entropy, namely, configurational, polar solvation and hydrophobic entropies. All of these contributions are evaluated by the restraint release (RR) approach. The calculated results shed an interesting light on major compensation effects in both the solvation and hydrophobic effect, and despite some overestimate, can provide very useful insight. The present study also helps in analyzing some problems with the widely used MM/PBSA approach.

The 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway for isoprenoid biosynthesis has come under increased scrutiny as a target for novel antimalarial, antibacterial and herbicidal agents. 1-Deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) is a key enzyme of the pathway that catalyzes the rearrangement and nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reduction of 1-deoxy-D-xylulose 5-phosphate (DXP) to MEP. The unique properties of DXR make it a remarkable and rational target for drug design. First, it is a vital enzyme for synthesis of isoprenoids in algae, plants, several eubacteria including the pathogenic bacteria like Bacillus anthracis, Helicobacter pylori, Yersinia pestis, Mycobacterium tuberculosis and the malarial parasite, Plasmodium falciparum. Second, there are no functional equivalents to DXR in humans, making it an attractive target for therapeutic intervention. Third, DXR appears to be a valid target and the results from fosmidomycin (1), the only available DXR inhibitor under clinical trials, suggests synergistic effects with the lincosamide antibiotics, lincomycin and clindamycin. Despite drug design efforts in this area, no successful drug specifically designed to inhibit DXR has emerged yet. This review summarizes the recent and promising developments with respect to the current knowledge of the MEP pathway with emphasis on the understanding of the structure and the catalytic mechanism of the DXR enzyme and the global quest for therapeutically useful inhibitors of DXR.

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