were performed Lenalidomide without any restrains on these two systems in the NPT ensemble at a temperature of 300 K and a pressure of 1 atm. During the simulations, a time step of 2 fs was used, periodic boundary conditions were employed and all electrostatic interactions were calculated using a particle mesh Ewald method with a dielectric constant of unity. A 10.0 A˚ cutoff was used to calculate the direct space sum of PME. The SHAKE algorithm was used to restrain bond lengths involving hydrogen atoms. Based on the constructed initial structures of HIV 1 IN–vDNA and HIV 1 IN–vDNA–RAL complexes, MD simulations were performed to obtain the reasonable and stable complexes. For the two systems, the equilibration of MD trajectories was monitored by the root mean square displacement values of Ca atoms with respect to the starting structure shown in Figure 3.
Relative to the small RMSD values for the residues of the CCD, the RMSD values observed for two full length complexes show a relatively wider range, suggesting that the significant domain movements are involved. Actually, this reased structural flexibility of two systems is attributed to the existence of more flexible subdomains such as the domain Caspase Pathway linker regions . However, for the ternary system, the RMSD values appear to be more stable, apparently due to the presence of the binding to RAL. Most notably, the time evolution of the RMSD values shown in Figure 3c indicated that the 140s loop flexibility was significantly affected by RAL binding.
To extend this analysis, the root mean square fluctuations values calculation were also performed on the all atom MD simulations, and the results illustrated that the presence of RAL indeed induced a great change in RMSF variation in the 140s loop region. These phenomena imply that binding of vDNA substrate imposes the proper configuration of domains objectified for the integration reaction to occur and the 140s loop in the active site shows high flexibility, yet when Interaction mechanism of vDNA with HIV 1 IN Energetic aspects of the interactions. The components of the binding free energies for the vDNA to HIV 1 IN and HIV 1 IN–RAL complex were evaluated by using the MM PBSA and MM GBSA methodologies. In parallel with the calculated RMSD values shown in Figure 3, the last 5 ns of the trajectories were regarded as stable and were used to extract 500 snapshots for the binding free energy calculation of the HIV 1 IN–vDNA and HIV 1 IN–vDNA–RAL complexes, respectively.
It should be noted that long time simulation studies were necessary to obtain the reliable binding free energy because of the large fluctuations observed in the computed free energies. The detailed contribution of various energy components based on MM PBSA and MM GBSA methods is given in Table 1. One of the advantages of MM PBSA and MM GBSA approaches is that it enables to decompose the free energy into identifiable such as Gln53, Val54, Lys156, Lys160, Arg187, and Arg263 from HIV 1 IN are strongly involved in the interaction with vDNA. Moreover, by comparing Figures 5a and 5b, we found that when RAL bind to the active site, it cannot influence the binding of vDNA to HIV 1 IN. On the other hand, the energetic contributions of each individual .