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« LigandScout 3.1 Overview 1. Help Overview 2. Introduction to LigandScout 2.1 What's New in LigandScout 3? 2.2 Installing and Starting LigandScout 2.3 Visual Semantics 2.4 LigandScout Graphical User Interface 3. File Handling, Data Management and Networking 3.1 Importing and Exporting Files 3.2 Retrieving PDB Complexes Online 3.3 Local and Shared Repository 3.4 Sessions 3.5 Networking 4. LigandScout Perspectives 4.1 Basic User Interface Modules 4.2 Structure-Based Modeling Perspective 4.3 Ligand-Based Modeling Perspective 4.4 Alignment Perspective 4.5 Screening Perspective 5. Introduction to Pharmacophore Modeling 5.1 Pharmacophore Modeling 5.2 Pharmacophore Feature Definitions 5.3 Editing a Pharmacophore Model 6. Structure-Based Pharmacophore Design 6.1 Structure-Based Pharmacophores 6.2 Creating Structure-Based Pharmacophores 7. Pharmacophore Alignment 7.1 Aligning Pharmacophores and Molecules 7.2 Shared Feature Pharmacophore 7.3 Merged Feature Pharmacophore 8. Ligand-Based Pharmacophore Design 8.1 Ligand-Based Pharmacophores 8.2 Creating Ligand-Based Pharmacophores 9. Virtual Screening 9.1 Virtual Screening in LigandScout 9.2 Preparing a Pharmacophore for Virtual Screening with External Applications 10. LigandScout Settings: Preferences 10.1 Structure-Based Modeling Settings 10.2 Ligand-Based Modeling Settings 10.3 Chemistry Settings 10.4 Library Screening Settings 10.5 Alignment Settings 10.6 Rendering Settings 10.7 Program and Network Settings A. Appendix A.1 LigandScout Menu Reference A.2 LigandScout Icons Reference A.3 LigandScout Keyboard Shortcuts A.4 LigandScout Mouse Bindings A.5 Network Administrator Guide A.6 Command Line Usage A.7 Scoring Function A.8 Calculation of MMFF94 Binding Enthalpies A.9 Primary Literature Index	Table of Contents 1. Help Overview 2. Introduction to LigandScout What's New in LigandScout 3? Installing and Starting LigandScout Visual Semantics LigandScout Graphical User Interface 3. File Handling, Data Management and Networking Importing and Exporting Files Retrieving PDB Complexes Online Local and Shared Repository Sessions Networking 4. LigandScout Perspectives Basic User Interface Modules Structure-Based Modeling Perspective Ligand-Based Modeling Perspective Alignment Perspective Screening Perspective 5. Introduction to Pharmacophore Modeling Pharmacophore Modeling Pharmacophore Feature Definitions Editing a Pharmacophore Model 6. Structure-Based Pharmacophore Design Structure-Based Pharmacophores Creating Structure-Based Pharmacophores 7. Pharmacophore Alignment Aligning Pharmacophores and Molecules Shared Feature Pharmacophore Merged Feature Pharmacophore 8. Ligand-Based Pharmacophore Design Ligand-Based Pharmacophores Creating Ligand-Based Pharmacophores 9. Virtual Screening Virtual Screening in LigandScout Preparing a Pharmacophore for Virtual Screening with External Applications 10. LigandScout Settings: Preferences Structure-Based Modeling Settings Ligand-Based Modeling Settings Chemistry Settings Library Screening Settings Alignment Settings Rendering Settings Program and Network Settings A. Appendix LigandScout Menu Reference LigandScout Icons Reference LigandScout Keyboard Shortcuts LigandScout Mouse Bindings Network Administrator Guide Command Line Usage Scoring Function Calculation of MMFF94 Binding Enthalpies Primary Literature Index
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Page designed & authored by G. Wolber

Inte:Ligand: Your partner for in-silico drug discovery

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« LigandScout 3.1 Overview

1. Help Overview

2. Introduction to LigandScout

2.1 What's New in LigandScout 3?
2.2 Installing and Starting LigandScout
2.3 Visual Semantics
2.4 LigandScout Graphical User Interface

3. File Handling, Data Management and Networking

3.1 Importing and Exporting Files
3.2 Retrieving PDB Complexes Online
3.3 Local and Shared Repository
3.4 Sessions
3.5 Networking

4. LigandScout Perspectives

4.1 Basic User Interface Modules
4.2 Structure-Based Modeling Perspective
4.3 Ligand-Based Modeling Perspective
4.4 Alignment Perspective
4.5 Screening Perspective

5. Introduction to Pharmacophore Modeling

5.1 Pharmacophore Modeling
5.2 Pharmacophore Feature Definitions
5.3 Editing a Pharmacophore Model

6. Structure-Based Pharmacophore Design

6.1 Structure-Based Pharmacophores
6.2 Creating Structure-Based Pharmacophores

7. Pharmacophore Alignment

7.1 Aligning Pharmacophores and Molecules
7.2 Shared Feature Pharmacophore
7.3 Merged Feature Pharmacophore

8. Ligand-Based Pharmacophore Design

8.1 Ligand-Based Pharmacophores
8.2 Creating Ligand-Based Pharmacophores

9. Virtual Screening

9.1 Virtual Screening in LigandScout
9.2 Preparing a Pharmacophore for Virtual Screening with External Applications

10. LigandScout Settings: Preferences

10.1 Structure-Based Modeling Settings
10.2 Ligand-Based Modeling Settings
10.3 Chemistry Settings
10.4 Library Screening Settings
10.5 Alignment Settings
10.6 Rendering Settings
10.7 Program and Network Settings

A. Appendix

A.1 LigandScout Menu Reference
A.2 LigandScout Icons Reference
A.3 LigandScout Keyboard Shortcuts
A.4 LigandScout Mouse Bindings
A.5 Network Administrator Guide
A.6 Command Line Usage
A.7 Scoring Function
A.8 Calculation of MMFF94 Binding Enthalpies
A.9 Primary Literature

Index

Structure-Based Modeling Settings

PDB Interpretation

The PDB Interpretation Settings allows for adjusting ligand interpretation and customization of properties of chemical features ( distance ranges , hydrogen bonding , metal binding , hydrophobicity and aromatic interactions ) used in the pharmacophore generation.

Figure 10.1. PDB interpretation

PDB Interpretation	Effect
Interaction cutoff threshold	Defines a sphere surrounding each non-hydrogen atom of the ligand. All non-hydrogen atoms in the environment which are within this sphere are considered as possible interaction partners during the pharmacophore generation process. (default: 7.00 Å)
Planarity PCA threshold	Defines the maximum out-of-plane deviation of parts of a molecule to be considered planar. General sets the threshold for acyclic molecule parts whereas Rings sets the threshold for cyclic molecule parts. Higher PCA threshold increases the out-of-plane tolerance resulting in an enhanced preference for sp ³ hybridized atoms. (default: General: 0.250 Å; Rings: 0.220 Å)
Intra ligand limit	Defines the maximum spacial distance between atoms of two molecules to be considered as a single ligand. Increasing this limit results in a preferred interpretation of two molecules to be seen as one ligand. (default: 2.00 Å)
Update HET dictionary	Updates the HET Dictionary from an online PDB resource. The HET dictionary is used to enhance the PDB interpretation in case the loaded data is incomplete (e.g. missing connect records, etc.)

Chemical Defaults

Effect

Acids and cases

If set true for the ligand or environment, the protonation states will be adjusted automatically after downloading or opening PDB structures. In fact, all single-bonded oxygens of acidic moieties will be deprotonated. For nitrogens which are double-bonded to two oxygens, one of the double-bonds will be replaced by a single bond, the nitrogen's charge will be set to +1 and the oxygen will be deprotonated. (default: enabled)

Distance Ranges

Figure 10.2. Distance ranges settings

Feature Distance	Effect
Feature-specific distance range	Defines the distance interval in which LigandScout considers hydrogen bonding by Hydrogen Bond Donor and Hydrogen Bond Acceptor features, hydrophobic interactions by Hydrophobic features, charge interactions by Ionizable features, metal binding interactions by Magnesium , Zinc , and IronBinding Locations , and aromatic interactions by Aromatic Plane features.
Core	Select the ligand-side feature for which the distance constraint should be set.
Env	Select the environment-side feature for which the distance constraint should be set. An interaction is only possible within the defined distance range. The environment is the part of the macromolecule that surrounds the ligand.
Current distance range	Shows the currently set distance range for the selected core-environment feature pair.
Min	Adjust the minimum distance range. (in Å)
Max	Adjust the maximum distance range (in Å).
Set Range	Sets the newly adjusted distance range for the selected core-environment feature pair.

Steric Constraints	Effect
Alpha C distance	Set the minimum and maximum distance (such that an excluded volume on an alpha carbon can be generated. If the alpha carbon has interactions with ligand atoms closer than the maximum distance and no other feature is closer than the minimum distance, then an excluded volume will be created on an alpha carbon. (default: Min: 2.0 Å; Max: 4.0 Å)
Alpha C exclusion tolerance	Sets the tolerance value which an excluded volume on an alpha carbon will have. (default: 1.00 Å)

Hydrogen Bonding

Figure 10.3. Chemical feature hydrogen bond settings

Angle ranges	Effect
sp ²	For an sp ² hydrogen bond donor atom. The angle between the vector (hbd atom, hydrogen) and vector (hydrogen, hba atom) must be below this threshold to be a valid hydrogen bond. (default: 50.00°)
sp ³	For an sp ³ hydrogen bond donor atom. The angle between the vector (hbd atom, hydrogen) and vector (hydrogen, hba atom) must be below this threshold to be a valid hydrogen bond. (default: 34.00°)
Acceptor	Calculate the weighted vector from the hydrogen bond accecptor atom to all of its neighbors. This mixed direction vector is inverted and checked against the vector (hydrogen bond acceptor atom, hydrogen bond donor atom). This angle must be below the specified threshold. (default: 85.00°)

Metal Binding

Figure 10.4. Chemical feature metal binding

Metal binding	Effect
Maximum binding direction deviation	Defines the maximum angle deviation from a ligating atoms idealized metal-binding axis. Lowering the value causes more restrictive handling of preferred binding direction deviations. (default: 120.00°)
Maximum binding symmetry deviation	Defines the maximum allowed relative binding length difference of a metal atom to two or more ligating atoms. This setting is only effective in case of chelating moieties like hydroxamates. The lower the value the more restrictive is the handling. (default: 0.75Å)

Hydrophobicity

Figure 10.5. chemical feature hydrophobicity settings

Hydrophobicity	Effect
Minimum thresholds	Defines the minimum hydrophobic threshold of rings, chains and groups to be considered as a hydrophobic moiety. Increasing the minimum threshold causes more restrictive handling of hydrophobicity characteristics, resulting in pharmacophores containing less hydrophobic features.
Surface accessibility threshold	Defines the minimum sterical accessability threshold for moieties to be considered as hydrophobic. The higher the threshold the more restrictive the feature identification will be.

Aromatic Interactions

Figure 10.6. Chemical feature aromatic interaction settings

Aromatic Interactions	Effect
Orthogonal center deviation	The minimum and maximum distance constraint two orthogonal plane feature center points (one from the core and the other from the environment) must meet. (default: Min: 0.0 Å; Max: 2.0 Å)
Parallel center deviation	The minimum and maximum distance constraint two parallel plane feature center points (one from the core and the other from the environment) must meet. (default: Min: 0.0 Å; Max: 2.0 Å)
Angle tolerance for pi-cation interactions	The angle constraint that must be met for the angle between vector (plane center, ion position) and plane normal vector to be a valid plane ion interaction feature. (default: 60.00°)
Angle tolerance for pi-pi interactions	Orthogonal sets the maximum angle the two normal vectors for two pi-pi orthogonal plane features may enclose to be a valid interaction. Parallel sets the maximum angle the two normal vectors for two Pi-Pi parallel plane features may enclose to be a valid interaction. (default: orthogonal: 20.00°; parallel: 20.00°)

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