Project ID: plumID:22.032
Name: Reciprocal barrier restraint. Application to path-meta-eABF
Archive: https://zenodo.org/record/7030287/files/CRL-VHL-degrader-SMARCA2-ring-closure-path-meta-eabf.zip
Category: methods
Keywords: restraint, upper wall, lower wall, path colvar, meta-eABF, metadynamics, DRR, protein conformational transition, PROTAC
PLUMED version: 2.7
Contributor: Istvan Kolossvary
Submitted on: 29 Aug 2022
Publication: I. Kolossváry, W. Sherman, Comprehensive Approach to Simulating Large Scale Conformational Changes in Biological Systems Utilizing a Path Collective Variable and New Barrier Restraint. The Journal of Physical Chemistry B. 127, 5214–5229 (2023)

PLUMED input files

File Compatible with
plumed.dat tested on v2.9 tested on master

Last tested: 26 Feb 2024, 07:17:40

Project description and instructions
To run this simulation you need OpenMM 7.6 or newer and the OpenMM-PLUMED plugin installed. To start the job run the following command line python run_path-meta-eabf.py n_steps do_relax do_plumed. For example, python run_path-meta-eabf.py 50000 1 0 will minimize the system and run 50,000 steps of MD relaxation while python run_path-meta-eabf.py 5000000 0 1 will read the checkpoint file and continue 5 million steps of meta-eABF simulation using the path colvar representing the opening and closing of the full CRL-VHL-degrader-SMARCA2 ring complex. NOTE. The current implementation of the PATHMSD action has a flaw that results in numerical instability due to computing exp(-lambda*(it.distance)) with very large lambda values, without scaling. I highly recommend to make the following simple edit to PathMSDBase.cpp to introduce proper scaling, as follows. $ diff PathMSDBase.cpp PathMSDBase.cpp-orig 275d274 < double min_distance=1e10; 281,285c280 < if(it.distance < min_distance) min_distance=it.distance; < } < < for(auto & it : imgVec) { < it.similarity=exp(-lambda*(it.distance - min_distance)); --- > it.similarity=exp(-lambda*(it.distance)); 293c288 < val_z_path->set(-(1./lambda)*std::log(partition) +min_distance); --- > val_z_path->set(-(1./lambda)*std::log(partition));

Submission history
[v1] 29 Aug 2022: original submission

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