Hi Joseph, In addition to what Elaine said, unless we are talking about a very small number of torsion angles (or very sparse angle sampling) you quickly get into an intractable combinatorial explosion of states. --Eric Eric Pettersen UCSF Computer Graphics Lab
On Feb 5, 2026, at 8:45 AM, Elaine Meng via ChimeraX-users <chimerax-users@cgl.ucsf.edu> wrote:
Just about any molecular modeling program can be used to step-change torsion angles, if that's what you meant, but Chimera and ChimeraX do not calculate free energy. Any number you get from a single-point "energy" evaluation or subsequent minimization is not going to represent the free energy, so in my opinion, it is unlikely to be a useful approach.
Please do not send general questions/comments to the bug-report address. I removed it from the recipients.
Regards, Elaine ----- Elaine C. Meng, Ph.D. UCSF Chimera(X) team Resource for Biocomputing, Visualization, and Informatics Department of Pharmaceutical Chemistry University of California, San Francisco
On Feb 5, 2026, at 7:35 AM, Boyle, Joseph J via ChimeraX-users <chimerax-users@cgl.ucsf.edu> wrote:
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
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