A2. Protein Sampling (for Cryptic Pockets): Calculate Normal Modes¶
Category Paths
Follow one of these paths in the Orion user interface, to find the floe.
Product-based/Molecular Dynamics
Solution-based/Virtual-screening/Target Preparation
Solution-based/Hit to Lead/Target Preparation/Enhanced Sampling
Solution-based/Target Identification/Target Preparation/Pocket Detection
Solution-based/Hit to Lead/Target Preparation/Cryptic Pocket Detection
Role-based/Computational Chemist
Task-based/Target Prep & Analysis/Pocket Detection
Description
This floe identifies the normal modes associated with the input conformation and generates a dataset containing top 20 normal modes with high ‘Mode Collectivity’ and ‘Variance’. These modes are mapped on a design unit that can be viewed via the 3D or Analyze pages on Orion. One or two selected normal modes are intended as input to a ‘Protein Sampling’ Floe, and we suggest choosing from modes with a high ‘Mode Collectivity’ value.
Promoted Parameters
Title in user interface (promoted name)
Inputs
Solvated and Equilibrated Design Unit (in): This is the ‘Solvated and Equilibrated Design Unit’ output dataset from the ‘A1. Protein Sampling (for Cryptic Pockets): Solvate and Equilibrate Target Protein’ floe.
Required
Type: data_source
Outputs
Output Dataset (out): Output dataset to write to.
Required
Type: dataset_out
Default: Protein Normal Modes Dataset
Failure Report (fail_report): Output report to generate upon failure.
Type: string
Default: Protein Normal Mode Failure Report
System Parameters
Selection String (selstr): Selection strings for selecting a subset of the structure to be used to perform the ANM calculations. Use the output pdb file from the A1. Protein Sampling (for Cryptic Pockets): Solvate and Equilibrate Target Protein floe as a reference when selecting the residue and chains for the selection string(s). The general syntax follows “[chain_id]:[from_res_num]~[to_res_num]”. In practice this would look like “A:1~150” when selecting residues 1 to 150 on chain A of the input protein. Multiple residue ranges are supported by inputting multiple entries. See tutorial for more examples.
Type: string
Advanced System Parameters
Subsystem Analysis (subsystem_method):
Method for subsystem analysis if a subsystem is specified. Slice: simply extract the subsystem portion of the motion. Reduce: calculate subsystem’s motion while taking account of the effects from the environment. This method is identical to the “Slice” method if the model is EDA/PCA.
Type: string
Default: Reduce
Choices: [‘Slice’, ‘Reduce’]
Subsystem Selection String (substr): Selection strings for selecting the subsystem for performing system-environment analysis. Use the output pdb file from the A1. Protein Sampling (for Cryptic Pockets): Solvate and Equilibrate Target Protein floe as a reference when selecting the residue and chains for the selection string(s). The general syntax follows “[chain_id]:[from_res_num]~[to_res_num]”. In practice this would look like “A:1~150” when selecting residues 1 to 150 on chain A of the input protein. Multiple residue ranges are supported by inputting multiple entries.
Type: string
ANM Parameters
Spring Constant (gamma):
Spring Constant of the elastic network.
Type: decimal
Default: 1.0
Cutoff Distance (Å) (cutoff):
Cutoff distance for pairwise interactions.
Type: decimal
Default: 15.0