Analyzer

  • In PaCS-MD, the analyzer is a component that evaluates the snapshot of each trajectory in each cycle and ranks them based on the evaluation type specified in the input file.
  • Some of the top ranked frames become the initial structure of each replica in the next cycle.
  • You can use the following evaluation functions by setting the #analyzer keyword in your input file. Depending on the phenomenon of interest, the appropriate type must be selected.
  • If you do not find a type that meets your purpose, you can implement it yourself by setting type = template.
  • The following are some commonly used evaluation types.

Content

Dissociation

  • Evaluate snapshots of each trajectory so that the centers of mass of the two selected groups are far apart.
  • Usage Example
    • Ligand dissociating from a protein
    • Separate the distance between the two domains of a protein
  • For more information, see here.
  • See here for an example input file.
Papers 
[1] Protein-Ligand Dissociation Simulated by Parallel Cascade Selection Molecular Dynamics, https://doi.org/10.1021/acs.jctc.7b00504
[2] Dissociation Process of a MDM2/p53 Complex Investigated by Parallel Cascade Selection Molecular Dynamics and the Markov State Model, https://doi.org/10.1021/acs.jpcb.8b10309
[3] Binding free energy of protein/ligand complexes calculated using dissociation Parallel Cascade Selection Molecular Dynamics and Markov state model, https://doi.org/10.2142/biophysico.bppb-v18.037
[4] High pressure inhibits signaling protein binding to the flagellar motor and bacterial chemotaxis through enhanced hydration, https://doi.org/10.1038/s41598-020-59172-3
[5] Dissociation Pathways of the p53 DNA Binding Domain from DNA and Critical Roles of Key Residues Elucidated by dPaCS-MD/MSM, https://doi.org/10.1021/acs.jcim.1c01508

Association

  • Evaluate snapshots of each trajectory so that the centers of mass of the two selected groups are close together.
  • Usage Example
    • Bringing a ligand closer to a protein
    • Bringing two domains of a protein closer together
  • For more information, see here.
  • See here for an example input file.
Papers

Target

  • Evaluate snapshots of each trajectory so that the RMSD from the reference structure becomes smaller.
  • Usage Example
    • Finding transitions between two known structures.
  • Evaluate to follow the reference structure using RMSD.
  • For more information, see here.
  • See here for an example input file.
Papers 
[1] Parallel cascade selection molecular dynamics (PaCS-MD) to generate conformational transition pathway, https://doi.org/10.1063/1.4813023

RMSD

  • Evaluate snapshots of each trajectory so that the RMSD from the reference structure becomes larger.
  • Usage Example
    • Sampling a wide range of structures
    • Sampling a wide range of ligand binding modes
  • For more information, see here.
  • See here for an example input file.
Papers 
[1] Inhibition of the hexamerization of SARS-CoV-2 endoribonuclease and modeling of RNA structures bound to the hexamer, https://doi.org/10.1038/s41598-022-07792-2

EdgeExpansion

  • Evaluate snapshots of each trajectory so that the frame forms the convex hull of the 4-dimentional principal component space(PCs).
  • Usage Example
    • Sampling a wide range of phase space without knowing the reference structure
  • For more information, see here.
  • See here for an example input file.
Papers 
[1] Edge expansion parallel cascade selection molecular dynamics simulation for investigating large-amplitude collective motions of proteins, https://doi.org/10.1063/5.0004654

A_D

  • Evaluate snapshots of each trajectory so that the distance between the centers of mass of the two selected groups fluctuates significantly within a certain range.
  • Usage Example
    • Observing large movements of proteins, such as opening and closing.
    • Observing the binding and unbinding of ligands.
  • For more information, see here.
  • See here for an example input file.
Papers 
[1] Kinetic Selection and Relaxation of the Intrinsically Disordered Region of a Protein upon Binding, https://doi.org/10.1021/acs.jctc.9b01203

Template

  • Evaluate snapshots of each trajectory using a user-defined evaluation function.
  • Additional variables can be specified in input.toml
  • Usage Example
    • If you want to use a different evaluation function than the ones provided.
  • For more information, click here