Interaction of I50V Mutant and I50L/A71V Double Mutant HIV-Protease with Inhibitor TMC114 (Darunavir): Molecular Dynamics Simulation and Binding Free Energy Studies

In the present work, the binding of inhibitor TMC114 (darunavir) to wild-type (WT), single (I50V) as well as double (I50L/A71V) mutant HIV-proteases (HIV-pr) was investigated with all-atom molecular dynamics (MD) simulations as well as molecular mechanic-Poisson–Boltzmann surface area (MM-PBSA) calculation. For both the apo and complexed HIV-pr, many intriguing effects due to double mutant, I50L/A71V, are observed. For example, the flap–flap distance and the distance from the active site to the flap residues in the apo I50L/A71V-HIV-pr are smaller than those of WT- and I50V–HIV-pr, probably making the active site smaller in volume and closer movement of flaps. For the complexed HIV-pr with TMC114, the double mutant I50L/A71V shows a less curling of the flap tips and less flexibility than WT and the single mutant I50V. As for the other previous studies, the present results also show that the single mutant I50V decreases the binding affinity of I50V–HIV-pr to TMC, resulting in a drug resistance; whereas the double mutant I50L/A71V increases the binding affinity, and as a result of the stronger binding, the I50L/A71V may be well adapted by the TMC114. The energy decomposition analysis suggests that the increase of the binding for the double mutant I50L/A71V–HIV-pr can be mainly attributed to the increase in electrostatic energy by −5.52 kacl/mol and van der Waals by −0.42 kcal/mol, which are canceled out in part by the increase of polar solvation energy of 1.99 kcal/mol. The I50L/A71V mutant directly increases the binding affinity by approximately −0.88 (Ile50 to Leu50) and −0.90 (Ile50′ to Leu50′) kcal/mol, accounting 45% for the total gain of the binding affinity. Besides the direct effects from the residues Leu50 and Leu50′, the residue Gly49′ increases the binding affinity of I50L/A71V–HIV-pr to the inhibitor by −0.74 kcal/mol, to which the electrostatic interaction of Leu50's backbone contributes by −1.23 kcal/mol. Another two residues Ile84 and Ile47′ also increase the binding affinity by −0.22 and −0.29 kcal/mol, respectively, which can be mainly attributed to van der Waals terms (Δ<i>T</i>_vdw = −0.21 and −0.39 kcal/mol)

Overall trust fluctuation (each minute).

In the field of Internet of Things (IoT), terminal security has always been an extremely important independent research topic. In the terminal security research, in addition to the security enhancement of terminal entities, the security status evaluation of terminal security has also become an independent subset of the security research in the IoT field. However, it should also be noted that the security attributes of IoT terminals can include many aspects, so judging the security of IoT terminals based on the overall security form is not enough for the security of terminal entities. This paper introduces the concept of volatility from the overall situation assessment to the meta attributes that constitute the overall security situation, and preliminarily realizes the construction of a concise model based on historical data to judge the meta attributes that may affect the overall security in the future. At the same time, a concise verification system is built based on the application scenario of the power IoT terminals currently under research to preliminarily realize trend prediction, further expand the trust evaluation of IoT terminals, and clarify the direction of further research.</div

Symbol definition table used in this paper.

In the field of Internet of Things (IoT), terminal security has always been an extremely important independent research topic. In the terminal security research, in addition to the security enhancement of terminal entities, the security status evaluation of terminal security has also become an independent subset of the security research in the IoT field. However, it should also be noted that the security attributes of IoT terminals can include many aspects, so judging the security of IoT terminals based on the overall security form is not enough for the security of terminal entities. This paper introduces the concept of volatility from the overall situation assessment to the meta attributes that constitute the overall security situation, and preliminarily realizes the construction of a concise model based on historical data to judge the meta attributes that may affect the overall security in the future. At the same time, a concise verification system is built based on the application scenario of the power IoT terminals currently under research to preliminarily realize trend prediction, further expand the trust evaluation of IoT terminals, and clarify the direction of further research.</div

Network architecture.

In the field of Internet of Things (IoT), terminal security has always been an extremely important independent research topic. In the terminal security research, in addition to the security enhancement of terminal entities, the security status evaluation of terminal security has also become an independent subset of the security research in the IoT field. However, it should also be noted that the security attributes of IoT terminals can include many aspects, so judging the security of IoT terminals based on the overall security form is not enough for the security of terminal entities. This paper introduces the concept of volatility from the overall situation assessment to the meta attributes that constitute the overall security situation, and preliminarily realizes the construction of a concise model based on historical data to judge the meta attributes that may affect the overall security in the future. At the same time, a concise verification system is built based on the application scenario of the power IoT terminals currently under research to preliminarily realize trend prediction, further expand the trust evaluation of IoT terminals, and clarify the direction of further research.</div

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In the field of Internet of Things (IoT), terminal security has always been an extremely important independent research topic. In the terminal security research, in addition to the security enhancement of terminal entities, the security status evaluation of terminal security has also become an independent subset of the security research in the IoT field. However, it should also be noted that the security attributes of IoT terminals can include many aspects, so judging the security of IoT terminals based on the overall security form is not enough for the security of terminal entities. This paper introduces the concept of volatility from the overall situation assessment to the meta attributes that constitute the overall security situation, and preliminarily realizes the construction of a concise model based on historical data to judge the meta attributes that may affect the overall security in the future. At the same time, a concise verification system is built based on the application scenario of the power IoT terminals currently under research to preliminarily realize trend prediction, further expand the trust evaluation of IoT terminals, and clarify the direction of further research.</div

Fluctuation of each meta attribute under the premise of large fluctuation.

Fluctuation of each meta attribute under the premise of large fluctuation.</p

The value of each meta attribute trust value under the premise of large fluctuations.

The value of each meta attribute trust value under the premise of large fluctuations.</p

Topology of simulation evaluation.

In the field of Internet of Things (IoT), terminal security has always been an extremely important independent research topic. In the terminal security research, in addition to the security enhancement of terminal entities, the security status evaluation of terminal security has also become an independent subset of the security research in the IoT field. However, it should also be noted that the security attributes of IoT terminals can include many aspects, so judging the security of IoT terminals based on the overall security form is not enough for the security of terminal entities. This paper introduces the concept of volatility from the overall situation assessment to the meta attributes that constitute the overall security situation, and preliminarily realizes the construction of a concise model based on historical data to judge the meta attributes that may affect the overall security in the future. At the same time, a concise verification system is built based on the application scenario of the power IoT terminals currently under research to preliminarily realize trend prediction, further expand the trust evaluation of IoT terminals, and clarify the direction of further research.</div

Effect of Water on the Physical Properties of Quaternary Ammonium Salt–(dl)‑Lactic Acid Deep Eutectic Solvents

Deep eutectic solvents (DESs) are new green solvents, and quaternary ammonium salt acid DESs have been widely used in the field of analytical separation in recent years due to their low cost and environmental friendliness. In this work, the density, viscosity, and electrical conductivity of binary mixtures containing three quaternary ammonium salt–(dl)-lactic acid DESs with H2O were determined. The average molar volume, excess molar volume, and viscosity deviation of the DESs’ aqueous solutions trends were computed. The viscous flow activation energy of DESs’ aqueous solutions was derived using the Arrhenius equation. The DESs’ physical properties are significantly influenced by their structure, temperature, and water content. The excess molar volume and viscosity deviation are negative over the entire concentration range, indicating a strong interaction between DESs and water. The variation of viscosity and electrical conductivity of the binary system with temperature conforms to the Vogel–Fulcher–Tammann (VFT) equation and shows an opposite trend, i.e., viscosity decreases and electrical conductivity increases with increasing temperature. The VFT equation can be conveniently applied to the aqueous solutions of DESs

Spatial distribution of the estimated regression coefficients of the GWR model for the coupled coordination level of urban quality and technology innovation.

Spatial distribution of the estimated regression coefficients of the GWR model for the coupled coordination level of urban quality and technology innovation.</p