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 ________________________________ From: Timothy Springer via ChimeraX-users <chimerax-users@cgl.ucsf.edu> Sent: 05 February 2026 13:42 To: chimerax-bugs@cgl.ucsf.edu <chimerax-bugs@cgl.ucsf.edu>; ChimeraX Users Help <chimerax-users@cgl.ucsf.edu> Subject: [chimerax-users] Scenes This email from chimerax-users@cgl.ucsf.edu originates from outside Imperial. Do not click on links and attachments unless you recognise the sender. If you trust the sender, add them to your safe senders list<https://spam.ic.ac.uk/SpamConsole/Senders.aspx> to disable email stamping for this address. Scenes has a bug with centroids in a .cxc file. When I omit the centroids, scenes works fine. 8 hydrogen bonds found define centroid #1/A:214@CD1,CD2,CE1,CE2,CG,CZ radius 0.01 Centroid 'centroid' placed at [216.18133333 173.87416667 191.88966667] close #3.1 distance #1.3 #1/V:38@NE2 color black dashes 6 radius 0.04 Distance between a4b1_12G10_VCAMD1D3_core_122_real_space_refined_123.pdb #!1/V GLN 38 NE2 and centroid #1.3: 3.474Å define centroid #2/A:214@CD1,CD2,CE1,CE2,CG,CZ radius 0.01 Centroid 'centroid' placed at [215.46366667 173.33033333 193.372 ] show :Mg color :Ca yellow style :Ca, Mg sphere Changed 12 atom styles size :CA, Mg atomRadius +0.5 Changed 12 atom radii color :Ca yellow color :Mg gray select clear windowsize 946 1210 view matrix camera 0.61619,-0.78632,0.04465,217.04,0.17445,0.080986,-0.98133,138.47,0.76803,0.61248,0.18708,205.73 view matrix models #1,1,0,0,0,0,1,0,0,0,0,1,0,#1.1,1,0,0,0,0,1,0,0,0,0,1,0,#1.2,1,0,0,0,0,1,0,0,0,0,1,0,#2,0.99998,0.0014978,0.0060567,-0.7471,-0.0012816,0.99937,-0.035532,7.7363,-0.0061061,0.035524,0.99935,-6.4316,#2.1,1,0,0,0,0,1,0,0,0,0,1,0,#2.2,1,0,0,0,0,1,0,0,0,0,1,0 scenes save vcam_inter scenes restore vcam_inter Traceback (most recent call last): File "/opt/sbgrid/i386-mac/chimerax/1.11/ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versions/3.11/lib/python3.11/site-packages/chimerax/ui/gui.py<http://ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versio...>", line 816, in dropEvent _open_dropped_file(self.session, p) File "/opt/sbgrid/i386-mac/chimerax/1.11/ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versions/3.11/lib/python3.11/site-packages/chimerax/ui/gui.py<http://ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versio...>", line 2202, in _open_dropped_file run(session, 'open %s' % FileNameArg.unparse(path)) File "/opt/sbgrid/i386-mac/chimerax/1.11/ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versions/3.11/lib/python3.11/site-packages/chimerax/core/commands/run.py<http://ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versio...>", line 49, in run results = command.run(text, log=log, return_json=return_json) ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ File "/opt/sbgrid/i386-mac/chimerax/1.11/ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versions/3.11/lib/python3.11/site-packages/chimerax/core/commands/cli.py<http://ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versio...>", line 3237, in run result = ci.function(session, **kw_args) ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ File "/opt/sbgrid/i386-mac/chimerax/1.11/ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versions/3.11/lib/python3.11/site-packages/chimerax/open_command/cmd.py<http://ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versio...>", line 132, in cmd_open models = Command(session, registry=registry).run(provider_cmd_text, log=log)[0] ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ File "/opt/sbgrid/i386-mac/chimerax/1.11/ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versions/3.11/lib/python3.11/site-packages/chimerax/core/commands/cli.py<http://ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versio...>", line 3237, in run result = ci.function(session, **kw_args) ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ File "/opt/sbgrid/i386-mac/chimerax/1.11/ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versions/3.11/lib/python3.11/site-packages/chimerax/open_command/cmd.py<http://ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versio...>", line 216, in provider_open models, status = collated_open(session, None, [data], data_format, _add_models, ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ File "/opt/sbgrid/i386-mac/chimerax/1.11/ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versions/3.11/lib/python3.11/site-packages/chimerax/open_command/cmd.py<http://ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versio...>", line 510, in collated_open return remember_data_format() ^^^^^^^^^^^^^^^^^^^^^^ File "/opt/sbgrid/i386-mac/chimerax/1.11/ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versions/3.11/lib/python3.11/site-packages/chimerax/open_command/cmd.py<http://ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versio...>", line 498, in remember_data_format models, status = func(*func_args, **func_kw) ^^^^^^^^^^^^^^^^^^^^^^^^^^^ File "/opt/sbgrid/i386-mac/chimerax/1.11/ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versions/3.11/lib/python3.11/site-packages/chimerax/core_formats/__init__.py<http://ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versio...>", line 48, in open return open_command_script(session, data, file_name, **kw) ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ File "/opt/sbgrid/i386-mac/chimerax/1.11/ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versions/3.11/lib/python3.11/site-packages/chimerax/core/scripting.py<http://ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versio...>", line 171, in open_command_script _run_commands(session, commands, directory = dirname(path), log = log) File "/opt/sbgrid/i386-mac/chimerax/1.11/ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versions/3.11/lib/python3.11/site-packages/chimerax/core/scripting.py<http://ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versio...>", line 184, in _run_commands run(session, cmd, log=log) File "/opt/sbgrid/i386-mac/chimerax/1.11/ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versions/3.11/lib/python3.11/site-packages/chimerax/core/commands/run.py<http://ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versio...>", line 49, in run results = command.run(text, log=log, return_json=return_json) ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ File "/opt/sbgrid/i386-mac/chimerax/1.11/ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versions/3.11/lib/python3.11/site-packages/chimerax/core/commands/cli.py<http://ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versio...>", line 3237, in run result = ci.function(session, **kw_args) ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ File "/opt/sbgrid/i386-mac/chimerax/1.11/ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versions/3.11/lib/python3.11/site-packages/chimerax/scenes/cmd.py<http://ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versio...>", line 61, in restore_scene session.scenes.restore_scene(scene_name) File "/opt/sbgrid/i386-mac/chimerax/1.11/ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versions/3.11/lib/python3.11/site-packages/chimerax/scenes/manager.py<http://ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versio...>", line 102, in restore_scene self.get_scene(scene_name).restore_scene() File "/opt/sbgrid/i386-mac/chimerax/1.11/ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versions/3.11/lib/python3.11/site-packages/chimerax/scenes/scene.py<http://ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versio...>", line 198, in restore_scene model.restore_scene(scene_data) File "/opt/sbgrid/i386-mac/chimerax/1.11/ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versions/3.11/lib/python3.11/site-packages/chimerax/atomic/structure.py<http://ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versio...>", line 273, in restore_scene Model.restore_scene(self, scene_data['model state']) ~~~~~~~~~~^^^^^^^^^^^^^^^ KeyError: 'model state' KeyError: 'model state' File "/opt/sbgrid/i386-mac/chimerax/1.11/ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versions/3.11/lib/python3.11/site-packages/chimerax/atomic/structure.py<http://ChimeraX-1.11.app/Contents/Library/Frameworks/Python.framework/Versio...>", line 273, in restore_scene Model.restore_scene(self, scene_data['model state']) ~~~~~~~~~~^^^^^^^^^^^^^^^ - Tim Timothy A. Springer, Ph.D. Latham Family Professor, Harvard Medical School and Boston Children's Hospital Founder, Institute for Protein Innovation

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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