Nov 22 2021 Feedback.
Contents
 
Introduction
Help Videos
Reference Guide
Getting Started
Protein Structure
Molecular Graphics
Slides & ActiveICM
Sequences & Alignments
Protein Modeling
Cheminformatics
Learn and Predict
Docking
Virtual Screening
MolScreen
3D Ligand Editor
 Setup Ligand and Receptor
 Preferences
 Display Options
 Score and Strain
 Edit Ligand
 Screen Replacement Group
 Scan
 Bioisostere Scan
 Dock or Minimize
 Dock Table
 Fragment Linking - Core Replacement
 Restraints
 Docking Templates
 Flexible Groups
 Refinement
 Multiple Receptor Docking
 Covalent Docking
 Dock to APF
 Save Docked Complex
 Export Docking Project
 Close Project
Tables and Plots
Local Databases
ICM-Scarab
KNIME
Tutorials
FAQs
 
Index
PrevICM User's Guide
15.4 Evaluate Ligand Score and Strain
Next

Video |

After you have edited a ligand and re-docked or minimized it you can evaluate the Score and Strain for the ligand. Ideally a good modification to your ligand will lower the score.

About the Score

  • LE_Score The lower the Score the better the predicted interaction.
  • RTCNN (Radial ant Topological Convolutional Neural Net) - you can read more about this score here. The lower the better the predicted interaction.
  • LigStrain = The strain of the ligand. Lower values = less strain.

About the Score in ICM versions older than 3.9

  • VlsScore = the ICM-VLS score used for ligand screening. The lower the Score the better the predicted interaction. VLS score is available with ICM-Pro + VLS and ICM-Chemist-Pro products. This score does not incorporate the strain of the ligand compared to the free state.
  • LigStrain = The strain of the ligand. Lower values = less strain.
  • Score = This score does incorporate ligand strain. Therefore it is VlsScore + LigStrain. The lower the Score the better the predicted interaction.

To evaluate the Score and Strain:

  • Click on the "Recalculate Binding Score Button".

About Strain If your docked ligand is strained e.g strain >3 then there are some things you can do to investigate the reason for this.

  1. Look at the relaxed ligand in the ligand editor - are there significant differences between relaxed and docked ligand
  2. Display the energy circles - does that give any clues. This will display simple torsion circles visualization is limited to localized torsion strain such as amide bonds twisted out of plane.
  3. Another way to discover where the strain stems from is to perform constrained cartesian relaxation (minimization) of the ligand and observe resulting movements:
To do this:
  • Make a copy of the ligand (molecule drop-down menu in workspace/Copy to another object)
  • Make the copy current (object drop-down/Set to current)
  • Perform minimization (Menu MolMechanics/Minimize/Cartesian)
Typically you will see strained portions of the ligand move towards their "relaxed" positions.

Note that sometime strain is "global" i.e. it originates from the existence of a significantly lower energy conformer that is substantially distinct from the bound conformation. This is not readily visualizable, but can be better understood via conformational analysis of the free ligand (i.e. menu Chemistry/Generate 3D Conformers…) and comparison of the bound conformation to the energy spectrum of free conformers. <>


Prev
Center
Home
Up
Next
Edit Ligand

Copyright© 1989-2020, Molsoft,LLC - All Rights Reserved.
This document contains proprietary and confidential information of Molsoft, LLC.
The content of this document may not be disclosed to third parties, copied or duplicated in any form,
in whole or in part, without the prior written permission from Molsoft, LLC.