Using nanopores for the single-molecule sequencing of proteins – similar to nanopore-based sequencing of DNA – faces multiple challenges, including unfolding of the complex tertiary structure of the proteins and enforcing their unidirectional translocation through nanopores. Here, we combine molecular dynamics (MD) simulations with single-molecule experiments to investigate the utility of SDS (Sodium Dodecyl Sulfate) to unfold proteins for solid-state nanopore translocation, while simultaneously endowing them with a stronger electrical charge. Our simulations and experiments probe that SDS-treated proteins show considerable loss of protein structure during the nanopore translocation. Moreover, SDS-treated proteins translocate through the nanopore in the direction prescribed by the electrophoretic force fue to the negative charge impaired by SDS. In summary, our results suggest that SDS causes protein unfolding while facilitating protein translocation in the direction of the electrophoretic force, both characteristics could bring great advantages for future protein sequencing applications using solid-state nanopores.
The 2013 Nobel Prize in Chemistry highlights how crucial computer simulations have become for many scientific and engineering fields. Nowadays, scientific progress is not only driven by the interplay of new experimental measurements and increasingly sophisticated theoretical frameworks, but also by an incredible toolbox of complex computational models meeting ubiquitously available computing power and data storage facilities. Quantum mechanical (QM) calculations can be condensed into molecular mechanics (MM) force fields and coupled QM/MM calculations can derive atomic and molecular properties of biomolecular or materials science systems with high accuracy. Pure MM simulations driven by Monte Carlo or molecular dynamics algorithms are widely applied in biological chemistry/physics and can investigate large biomolecular systems, such as proteins, DNA, or RNA. One coarse‐grained class of these models, native‐structure‐based or Go models, are based on energy landscape theory and the principle of minimal frustration. Herein, an ensemble of converging pathways guide protein folding on a funnel‐like shape of the entire energy landscape towards the native state. Simulations based on these ideas have been tremendously successful in explaining protein folding and function. Their history and recent application highlights are reviewed.
Drug utilization evaluation (DUE) is an essential component of pharmacoepidemiology, it describes the extent, nature and determinants of drug exposure. It is an ongoing, authorised and systematic quality improvement process, which is designed to review drug use and prescribing patterns, provide feedback of results to clinicians and health care provider. In this context, DUE of HMG-COA reductase inhibitors, the drug of choice for hypercholesterolemia and diseases pertaining to cardiovascular system was studied at MICU, ICCU in a tertiary care teaching hospital. A total of 150 patients were studied over six months period on DUE this includes number of statins, its dose, frequency, duration of treatment and indications. In our study, male genders were more in both ICCU (67.65%) and MICU (56.1%). Subsequently, rational use of Atorvastatin was found to be more in male patients. Further among HMG COA reductase inhibitors, Atorvastatin was the most prescribed statin in our study period. In addition to this, hypertension accounts as a major distributing risk factor (21%) secondary to patient age (37.7%). Overall, our study demonstrated the importance of DUE and DUE for HMG-COA reductase inhibitors in ICCU and MICU to validate rational use of drugs for minimizing the adverse drug reactions and better treatment outcome.
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