PMC:4706832 / 29340-32562
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4706832","sourcedb":"PMC","sourceid":"4706832","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4706832","text":"Molecular dynamics simulation study was carried out with the help of GROMACS package 4.5.3 to explore the stability of the complex structures. In particular, the parameter, RMSD, was examined from the trajectory file and used for analyzing the complex stability. RMSD investigation can give a thought of how much the three-dimensional structure has deviated over the time. The result is shown in Fig. 4. Native type ALK-crizotinib complex structure acquired ~0.34 nm at 1000 ps during the simulations, while mutant type ALK-crizotinib complex structure acquired ~0.28 nm of backbone RMSD at 1000 ps. On the other hand, native-type ALK-CID11562217 structure acquired ~0.18 nm of backbone RMSD while mutant-type ALK-CID11562217 complex structure acquired ~0.22 nm of backbone RMSD at 1000 ps. Between a period of 2000–5000 ps, native type ALK-crizotinib complex structure maintains a RMSD value of ~0.30 nm whereas mutant type ALK-crizotinib complex structure showed a deviation from ~0.25 to ~0.36 nm. In the virtual complex, native-type ALK-CID11562217 structure showed a RMSD value between ~0.18 and ~0.20 nm and mutant type ALK-CID11562217 complex structure maintains a RMSD value of ~0.24 nm. From the period of 5000–10,000 ps, native-type ALK-crizotinib complex structure maintains a RMSD value of ~0.34 nm while, mutant type ALK-crizotinib complex has deviated from ~0.32 to ~0.36 nm. On the contrary, native-type ALK-CID11562217 complex structure maintains a RMSD value of ~0.25 nm while mutant type ALK-CID11562217 complex structure maintains a RMSD value of ~0.20 to ~0.24 nm. From the beginning of 11,000 ps to the end of 15,000 ps, mutant type ALK-crizotinib complex structure showed higher deviation and attains a RMSD value of ~0.44 nm while native-type ALK-crizotinib complex structure maintains a RMSD value of ~0.23 nm. Mutant type ALK-CID11562217 complex structure maintains a RMSD value of ~0.25 nm in this simulation period. Between a period of 16,000–19,000 ps, native type ALK-crizotinib complex structure maintains a RMSD value of ~0.35 nm whereas mutant type ALK-crizotinib complex structure showed a deviation from ~0.43 to ~0.45 nm. For instance, native-type ALK-CID11562217 structure showed a RMSD value of ~0.25 nm and mutant type ALK-CID11562217 complex structure maintains a RMSD value of ~0.22 nm. At the end of 20,000 ps the mutant type ALK-crizotinib complex structure attained RMSD of ~0.40 nm and native type ALK-crizotinib complex structure attained RMSD of ~0.35 nm. This clearly indicates that ALK double mutation disturb the structural stability and also its function. It is worth stressing that native and mutant type ALK-CID 11562217 able to maintain a RMSD of ~0.24 nm. Overall, significant difference in RMSD value observed between the crizotinib and CID 11562217 complex system. The lesser RMSD value of CID 11562217 complex demonstrates the stable binding of CID 11562217 with both native and mutant type ALK structures.\nFig. 4 Root mean square deviations correspond to native-type ALK-crizotinib complex (black), mutant-type ALK-crizotinib complex (red), native-type ALK-CID11562217 complex (green) and mutant-type ALK-CID11562217 complex (blue) along the MD simulation at 300 K","divisions":[{"label":"label","span":{"begin":2964,"end":2970}}],"tracks":[]}