I have docked ~100 molecules using Surflex-Dock as well as AutoDock and prepared two lists (one for each docking program) based on their scores and energies. I have narrowed the list by identifying the docked conformation with suitable/preferred h-bond interactions of molecules with critical residues of receptor protein. There are some cases where the scores are too good, but h-bond interactions are not to my preference.There are also such cases where scores are very poor, but preferred h-bond interactions are found. The list includes ~40 molecules. MD simulation is a way to measure the stability of these complexes on the time scale. But MD for ~40 molecules is a tedious as well time consuming.
Is there a way to put a check on these docked conformations,so that I can have
Before starting the MD simulation, you will need to minimize the starting structure. By minimizing your structures first, you might be able to narrow the field according to your criteria of scoring functions and H-bonding.
You could do energy minimizations of your docked structures and then reapply your selection criteria to narrow the field for subsequent MD simulations.
Dear SIr,
You can filter your molecules by
1. Highest docking scores with respect to your standard molecule.
2. Best docking pose (low RMSD with respect to co-crystal / standard molecule pose)
3. To confirm the pose you can also perform MM-GBSA and Induced fit docking.
You can select only those molecules which have reproducible pose , interactions scores in MM-GBSA and IFD.
This is a judicious way can filter out the molecules for an MD simulation.
Thank you !
Dear Sabahhudin,
Apart from the above mentioned suggestions I would like to add few more to the list as per my understanding. Since u have 40 odd molecules and to reduce their count for MD simulations, U have to have take into account their availability and feasibility of synthesis (if applicable). In addition u are supposed to go through ADMET and biological assay calculations (if possible).
Dear Ahmed,
If you are unable to narrow down or filter your complexes, I think running a short simulation with all 40 and based on stabilization of system or evaluation of other parameters you can further filter tour list. I think this job would be too tedious but with short scripts it is possible.
Dear Patil,
Thank you for your valuable suggestion. I have peformed QM/MM nteraction energy calculations, but that was not very helpful. I think I will need to perform molecular dynamics for 2-5ns of each complex to evaluate the stability.
If the H bond interactions are critical in your studies and if the system reasonably stabilizes say for example 100 ps then max. number of H bonds formed can be a good criteria for filtering the list for long time simulations. Though for such criteria I don't find any suitable literature.
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