{"action":"created","issue":{"url":"https://api.github.com/repos/pandegroup/openmm/issues/1032","labels_url":"https://api.github.com/repos/pandegroup/openmm/issues/1032/labels{/name}","comments_url":"https://api.github.com/repos/pandegroup/openmm/issues/1032/comments","events_url":"https://api.github.com/repos/pandegroup/openmm/issues/1032/events","html_url":"https://github.com/pandegroup/openmm/issues/1032","id":94388879,"number":1032,"title":"Handling Zn2+ ions with AMBER forcefields","user":{"login":"jchodera","id":3656088,"avatar_url":"https://avatars.githubusercontent.com/u/3656088?v=3","gravatar_id":"","url":"https://api.github.com/users/jchodera","html_url":"https://github.com/jchodera","followers_url":"https://api.github.com/users/jchodera/followers","following_url":"https://api.github.com/users/jchodera/following{/other_user}","gists_url":"https://api.github.com/users/jchodera/gists{/gist_id}","starred_url":"https://api.github.com/users/jchodera/starred{/owner}{/repo}","subscriptions_url":"https://api.github.com/users/jchodera/subscriptions","organizations_url":"https://api.github.com/users/jchodera/orgs","repos_url":"https://api.github.com/users/jchodera/repos","events_url":"https://api.github.com/users/jchodera/events{/privacy}","received_events_url":"https://api.github.com/users/jchodera/received_events","type":"User","site_admin":false},"labels":[],"state":"open","locked":false,"assignee":null,"milestone":null,"comments":15,"created_at":"2015-07-10T20:49:04Z","updated_at":"2015-07-29T15:58:53Z","closed_at":null,"body":"(This is related to #726, but different enough to warrant a new issue.)\r\n\r\n@rafwiewiora in our lab has been working on ways to deal with the Zn2+ ions [found in ~10% of all PDB structures](http://dx.doi.org/10.1021/ic401072d).  In fixed charge forcefields Zn2+ ions are not easily treated as simple Lennard-Jones spheres with a 2+ charge because they generally are found in protein structures engaged with Cys or His residues in semicovalent bonds (of the sort we used to call dative bonds).  There was a desire to build in some way to treat these that would be rather universally applicable and less \"hacky\" than attaching them with springs.\r\n\r\nMuch to our delight, someone tackled this issue in 1999 with a [very clever approach for fixed-charge forcefields](http://dx.doi.org/10.1007/s008940050119).  His solution was to create four dummy atoms at the tetracoordinate sites around the Zn atom that had both small mass and charge, allowing the Cys and His residues (in their appropriate protonation states) to coordinate in the proper geometry.  The ZN+dummy molecule is held together with valence terms, and is still treated as a separate residue that replaces the Zn atom alone.  The AMBER parameters are available [on a website](http://www.mayo.edu/research/labs/computer-aided-molecular-design/projects/zinc-protein-simulations-using-cationic-dummy-atom-cada-approach).\r\n\r\nWe have tested this solution in OpenMM through AMBER and it seems to work very well for us, producing reasonable-looking, stable simulations even when we have weird clusters involving two Zn2+ atoms and shared bridging CYX residues.  \r\n\r\nWe're now looking at including this Zn2+ parameter set along with our conversion of all the AmberTools 15 parameters to OpenMM ffxml format so that users can transparently handle these zinc-containing proteins if they include the appropriate `amber-zinc.xml` file in their arguments to `ForceField`.\r\n\r\nHowever, we likely have to make some modifications to `ForceField` and/or `Modeller` in order to add in the dummy atoms in a plausible geometry, and are soliciting feedback on the most appropriate way to do this.  We could either\r\n* **Modify `Modeller.addExtraParticles` to add the dummy atoms.**  This would probably require the PDB file contain bond entries between Zn2+ and the corresponding heavy atoms of the residues coordinated to them (many do) to allow each of four dummy atoms to be placed along this line.\r\n* **Modify `Modeller.addHydrogens` to add these dummy atoms.**  We would add these to the hydrogen definition file and then modify `addHydrogens` to also consider the bonding to `S` atoms as a potential hydrogen bond acceptor.\r\n* **Something else altogether.**  Perhaps there is a class of these kinds of dummy atoms that could be treated by a separate piece of code?  Or we could have problem-specific code in the `<script>` portion of the forcefield definition, though I'm not sure quite how that would work.\r\n\r\nThoughts/ideas/suggestions?  10% of the PDB is a huge amount, so it would be great if we could deal with these systems in some way.  I know that AMOEBA will eventually provide a much better way of handling these coordinated Zn2+ atoms, but since charge transfer is an important part of this phenomenon, it may still require terms even beyond AMOEBA to treat properly."},"comment":{"url":"https://api.github.com/repos/pandegroup/openmm/issues/comments/125998436","html_url":"https://github.com/pandegroup/openmm/issues/1032#issuecomment-125998436","issue_url":"https://api.github.com/repos/pandegroup/openmm/issues/1032","id":125998436,"user":{"login":"rafwiewiora","id":12088757,"avatar_url":"https://avatars.githubusercontent.com/u/12088757?v=3","gravatar_id":"","url":"https://api.github.com/users/rafwiewiora","html_url":"https://github.com/rafwiewiora","followers_url":"https://api.github.com/users/rafwiewiora/followers","following_url":"https://api.github.com/users/rafwiewiora/following{/other_user}","gists_url":"https://api.github.com/users/rafwiewiora/gists{/gist_id}","starred_url":"https://api.github.com/users/rafwiewiora/starred{/owner}{/repo}","subscriptions_url":"https://api.github.com/users/rafwiewiora/subscriptions","organizations_url":"https://api.github.com/users/rafwiewiora/orgs","repos_url":"https://api.github.com/users/rafwiewiora/repos","events_url":"https://api.github.com/users/rafwiewiora/events{/privacy}","received_events_url":"https://api.github.com/users/rafwiewiora/received_events","type":"User","site_admin":false},"created_at":"2015-07-29T15:58:53Z","updated_at":"2015-07-29T15:58:53Z","body":"I played around and conclude that the AmberTool15 metal code is not useful for this at all - at least not as this stage / for zinc / for model we decided to use. It's mainly good for non-bonded (i.e. pure electrostatic) models and just does parametrization - and parametrizing for every different structure is what we are avoiding by using the dummy atom model. It takes Gaussian outputs, does RESP charges and the bit where OpenMM is implemented - it's energy minimization for induced dipole parameters. Might be useful if we need to do the electrostatic model for any other ions, but for now I'm leaving it. \r\n\r\nGoing to update on addExtraParticles / addHydrogens tweaking soon. "}}