I have docked several ligand and protein and few of them have an unfavorable bump interaction. When we dock protein and ligand in Autodock-vina, they give us several output like out_ligand_1, out_ligand_2, out_ligand_3, etc.
In my case, for the same ligand but different pose (different output 'out_ligand_x'), one of them has unfavorable bump interaction, and the others don't. But i chose output ligand based on the lowest binding affinity, and that one is the one that has unfavorable bump interaction. My actual question is, is it still valid if I continue the simulation despite of the unfavorable bump situation?
I wish anyone can give me an understanding explanation. Thank you in advance!
Autodock vina, and other docking programs, base their binding affinity calculation on scoring functions. Although this information is helpful, one should not base the choice of the solution pose only on this parameter, as each scoring function has its own pitfalls. In fact there are other characteristics which are important to assess. One of them is the orientation of the ligand within the protein's binding site. One should assess if the solution is giving an expected orientation (e.g., are important noncovalent interactions established?). Furthermore, clashes between ligand's and protein's atoms might point out that the given pose has problems, and, consequently, should not be chosen. Nevertheless, if the solution that better fits the expected orientation presents some clashes, these clashes can potentially be dealt with by employing an energy minimization protocol.
Hi, Luís M. C. Teixeira. Thank you very much for your useful explanation! So could we conclude that we should not choose the ligand protein pose that have an unfavorable bump interaction?
I have further questions. In my case, with those unfavorable bump interaction, the RMSD of the ligand least square fit to the protein is showing a high value more than 10A, but the RMSD of the backbone is ok. Could that be a cause of this problem?
You're welcome Citra Hasanah. You should be careful when choosing a docking solution pose, and try to stay away from poses that exhibit clashes. Nevertheless, depending on the case you might be force to choose a pose that has clashes.
The answer to the second question is exactly what you assumed. As the ligand's atoms are having clashes with the protein's atoms, the ligand undergoes orientation changes to try to reach one that is favorable (i.e., does not have clashes and establishes favorable interactions with the protein). Moreover, this would result in a ligand RMSd graph with high values. Concerning the backbone RMSd, this means that the clashes probably do not involve backbone atoms. Thus, the protein's backbone is stable (i.e., does not deviate significantly from the starting structure).
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