I have done the docking by using DOCK6 software and on the basis of good poses and grid score sorted out a good docked ligand conformation. Now I want to calculate the accurate or some what close to experimentally determined binding energy, so that I could filter more ligands and narrow down the result. Basically MD simulation is a good option, but for ligand having >13 rotatable bonds it might appear tedious to me and also time is limiting constraint for me.
One option could be to use Tsallis like statistics for the ligand and normal Boltzmann statistics for the rest of the system. This method is already implemented in CHARMM software. [1] Then you can recover back the Boltzmann statistics for ligand sampling using the re-weighting techniques.
Alternatively, you can also think doing metadynamics simulations, but it will depend on how stable your protein will be.
[1] https://www.researchgate.net/publication/5695519_Multiple_scaling_replica_exchange_for_the_conformational_sampling_of_biomolecules_in_explicit_water
Article Multiple scaling replica exchange for the conformational sam...
Dr Kamberaj, thanks for your interest and suggestion, but I don't have any idea about this metadynamics simulations, would you please like to help me with this technique?
The method you have it implemented in NAMD program, but also in others most likely, since it is a method well established for sampling rare events in md simulations. One of latest review is given in this link
http://iopscience.iop.org/0034-4885/71/12/126601/
Basically, the method adds a bias in potential energy function as a sum of Gaussians centred along the trajectory based on the past history until you soon have a flat potential energy function.
- Badges
- Science topic
- Similar topics
- Computer Science and Engineering
- Bioinformatics