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