Analyze Protein-Ligand MD

Category Paths

Follow one of these paths in the Orion user interface, to find the floe.

  • Product-based/Molecular Dynamics/GROMACS

  • Product-based/Molecular Dynamics/OpenMM

  • Role-based/Computational Chemist

  • Role-based/Medicinal Chemist

  • Task-based/Molecular Dynamics

  • Task-based/Affinity Prediction

  • Solution-based/Hit to Lead/Target Preparation/Generic MD simulation

  • Solution-based/Hit to Lead/Affinity Prediction/STMD

  • Solution-based/Small Molecule Lead-opt/Affinity

Description

  • Purpose:

    • This floe analyzes protein-ligand MD trajectories for pose stability.

  • Method Recommendations/Requirements:

    • The input dataset to this floe must be the output dataset from one of the other floes that run either bound state only or bound and unbound protein-ligand MD simulations. The dataset is expected to contain bound protein-ligand MD trajectories, and may also contain unbound trajectories, as produced by one of these floes:

      • Short Trajectory MD with Analysis

      • Bound Protein-Ligand MD

      • FE-NES for Binding Affinity Prediction

  • Expertise Level:

    • Regular

  • Compute Resource:

    • Minimal

  • Keywords:

    • MDAnalysis

  • Related floes:

    • Short Trajectory MD with Analysis

    • Bound Protein-Ligand MD

    • FE-NES for Binding Affinity Prediction

Trajectories from different starting poses of the same ligand are combined and analyzed collectively. One analysis is in terms of interactions between the ligand and the active site. Another looks at clustering the ligand positions in the protein active site after fitting the trajectory based on active site C-alpha atomss. Ensemble MMPBSA and ensemble BintScore calculations are carried out on the trajectory and are localized to the ligand clusters. An HTML Floe Report is generated for the top 100 ligands by ensemble MMPBSA score. Once the analysis is done, it generates a downloadable tarball in Amazon S3, which includes the analysis results in CSV files, the HTML Floe Report, ligand trajectories, and molecular structure files of cluster medians and averages of the protein-ligand complex.

Promoted Parameters

Title in user interface (promoted name)

Inputs

MD Dataset Reader (md): With default naming, this input will be named md_output or md_output_with_analysis (current) or MD_Bnd_Anlys/MD_Bnd and MD_Unb_Anlys/MD_Unb (legacy bound/unbound MD) in an upstream floe.

  • Required

  • Type: data_source

Outputs

MD Output Dataset (eq_out): Output dataset of bound/unbound MD simulations with trajectory analysis.

  • Required

  • Type: dataset_out

  • Default: md_output_with_analysis

MD Trajectory Analysis Report (md_floe_report): Title for the MD trajectory analysis floe report.

  • Type: string

  • Default: MD Trajectory Analysis

Failed Output Dataset (fail_out): Output dataset of failed calculations.

  • Required

  • Type: dataset_out

  • Default: Failed Output for Analyze Protein-Ligand MD