On Sun, 17 Mar 2019 at 21:27, Czodrowski, Paul < paul.czodrow...@tu-dortmund.de> wrote:
> Dear James, > > > > Ad 1) Paolo Tosco did an integration of openMM and also was able to run a > MD within Jupyter (partly covering (3)). Here is a link: > > > https://github.com/rdkit/UGM_2017/blob/master/Presentations/Tosco_RDKit_OpenMM_integration.pdf > > > I will share my experience with this because I also work on ligand binding affinity prediction. I do docking and MD-based equilibration of thousands of compounds in high throughput mode. I have written my own code to prepare the complexes and perform MD with explicit waters using AmberTools and OpenMM. Regarding force field parameters, I chose amber14sb (protein) and GAFF2 (ligand) because they are the current AMBER defaults and hence the most popular. Although protein force fields have reached a stage of (almost) perfection, ligand force fields are far from that. I have seen many compounds with wrong geometries after MD (distorted aromatic rings, out-of-aromatic place protons, etc.). To this end, I decided to write a script that reads an optimized ligand geometry and copies the equilibrium bond angles, dihedrals and bond lengths to the frcmod file in order to even out some of the problems. In the future, I will think about how I can also calculate fast and copy the force constants. Once I finish it I will make it open source on github so everybody can use it. I have never used Paolo Tosco's integration of OpenMM in RDKit as I had already written my code when I first saw his presentation in 2017. However, I guess that one could do similar simulations using his code with less effort. I use the MMFF only for ligand energy minimization in vacuo. For MD as already mentioned, I use amber14sb+GAFF2. I don't know what kind of interaction energies Jim Metz had in mind, but pure MM interaction energies can be misleading. You need to add the solvation/desolvation energy term to get meaningful results, namely MM/GBSA type of calculations would be more suitable, in which case you need protein and ligand force field parameter files and that's where my script will come in handy. I am also looking forward to seeing more SBDD integration to RDKit and I am happy to contribute code. With best regards, Thomas Evangelidis -- ====================================================================== Dr Thomas Evangelidis Research Scientist IOCB - Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences <https://www.uochb.cz/web/structure/31.html?lang=en> Prague, Czech Republic & CEITEC - Central European Institute of Technology <https://www.ceitec.eu/> Brno, Czech Republic email: teva...@gmail.com website: https://sites.google.com/site/thomasevangelidishomepage/
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