I am working on computationally understanding the active and inactive conformations of some proteins. Simulating the inactive conformation from the active conformation is reported in literature by performing enhanced sampling MD studies, like Metadynamics, REMD etc., in which energy is added in particular co-ordinates called collective variables. This makes it slightly biased.
If I run unbiased atomistic molecular dynamics simulations of several microseconds, will my protein explore the conformational space by crossing the energy barriers? Or will the system be eternally stuck in a local minimum which it first reaches?
Hi Rajiv,
It depends on the system you are studyng, some systems dont show important conformational changes in the microsecond or even in the milisecond time scale not only because they get trapped in a local minimum but also perhaps the conformational change is coupled to protonation or deprotonation or by some physicochemical conditions (pH or temperature). Therefore, before planning a computational experiment you need to search enought informatation about your system to propose the experiment.
If you ask me, I prefer run unbiased atomistic molecular dynamics simulation in the microsecond time scale, than biased methods for the reasons that you mentioned.
Thanks Drs. Abel and Bello, for your responses.
This question was stuck in mind for a while [like the protein is stuck in the local minimum :) ], and your replies were insightful.
Deaer Rajiv,
It is unlikely by using just molecular dynamic simulations (due to time-scale of the MD similations)/ However it might be possible by using other simulations (corse grained, finite elements ..)
Regards;
Joseph
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