I used to be involved in Molecular Dynamics (MD) simulations. It struck me that our central question - whether a ligand could fit in a cavity of an active site allowing for induced fit / protein flexibility - i.e. a larger active site than the unliganded crystal structure - could be answered more efficiently.

Specifically, MD is essentially intended to simulate thermal motions and basically increments bond angles. Whereas we were really asking about energy of some conformations (the ones with the enlarged active site). Indeed there are similar approaches in the literature e.g. Markov Monte Carlo - so it's not crazy ! This approach would promise to be much more computationally efficient than MD.

I am wondering if it is possible to use ChimeraX (or Chimera) to step-change the bond angles to enlarge the active site and recalculate energy and ligand dock - possibly in Python using a reiterative script ?

Hope my description is clear ?

Joseph J. Boyle

B.Sc.(Pharmacol. Hons Class I Glasgow), M.B.Ch.B.(with Hons Glasgow), Ph.D. (Cambridge), F.R.C.Path.(Histopath.),

Professor of Chemical Systems Pathology

National Heart and Lung Institute

Deputy Lead for Information Governance Faculty of Medicine

Imperial College London

Address:

Office 513

National Heart and Lung Institute 

Dr Victor Phillip Dahdaleh Building (VPD Building)

Imperial College London, Hammersmith Campus

Du Cane Rd

London 

W12 0NN

UK