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This module calculates the value of the octanol-water partition coefficient – LogP. Reliability of predictions is quantitatively estimated via the calculation of the Reliability Index value.
This module calculates the value of the octanol-water partition coefficient – LogP. Reliability of predictions is quantitatively estimated via the calculation of the Reliability Index value.
...
<br />
<br />


===Features===
===Features===
* ...
* Calculate the octanol-water partition coefficient for a wide range of neutral compounds under standard conditions, at 25°C
* Calculations are provided with 95% confidence intervals, or reliability Index (RI)
* Review bioconcentration factor (BCF) and the adsorption coefficient (Koc)
* Evaluate Rule-of-5 compliance
* Train the model with experimental values to improve predictions for proprietary chemical space
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[[Image:acdlogp_classic.png|center]]
[[Image:acdlogp_classic.png|center]]
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# Species: rat, mouse.<br>Administration type: intraperitoneal, oral, intravenous, subcutaneous.
# LogP prediction obtained using ACD/Labs LogP calculation algorithm.
# Predicted LD50 in mg/kg
# ...
# Reliability index (RI):<br>RI < 0.3 – Not Reliable,<br>RI in range 0.3-0.5 – Borderline Reliability,<br>RI in range 0.5-0.75 – Moderate Reliability,<br>RI >= 0.75 – High Reliability
<br>
# Up to 5 most similar structures in the training set. The records include structure name, experimental value and similarity index. This index is based on QSAR analysis of logLD50 data. Similarity index varies from zero to unity. Only compounds with similarity index greater than 0.5 are presented.
# Click the tab to browse for similar structures from various administration types. If no similar structures are found, the tab is disabled.<br>
 
 
# Lipophilic parts of the molecule are highlighted in green, hydrophilic groups in red, and the intensity of the color indicates the predicted degree of lipophilicity or hydrophilicity of an atom or a substructure
# LogP predictions obtained using Two different LogP calculation algorithms (AB/LogP 2.0 and ACD/Labs) are provided. AB/Log 2.0 predictions are supplemented by the assessment of prediction reliability by the means of calculated Reliability Index value
# Up to 5 most similar drug-like structures with experimental parameters
 
'''Note:''' Prediction reliability classification according to Reliability Index (RI) values:
* RI < 0.3 – Not Reliable,
* RI in range 0.3-0.5 – Bordeline Reliability,
* RI in range 0.5-0.75 – Moderate Reliability,
* RI >= 0.75 – High Reliability


<br />


=== ACD/LogP GALAS ===
=== ACD/LogP GALAS ===
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[[Image:acdlogp_galas.png|center]]
[[Image:acdlogp_galas.png|center]]
<br />
<br />
# Species: rat, mouse.<br>Administration type: intraperitoneal, oral, intravenous, subcutaneous.
# Lipophilic parts of the molecule are highlighted in green, hydrophilic groups in red, and the intensity of the color indicates the predicted degree of lipophilicity or hydrophilicity of an atom or a substructure.
# Predicted LD50 in mg/kg
# LogP prediction obtained using GALAS modeling methodology.
# Reliability index (RI):<br>RI < 0.3 – Not Reliable,<br>RI in range 0.3-0.5 – Borderline Reliability,<br>RI in range 0.5-0.75 – Moderate Reliability,<br>RI >= 0.75 – High Reliability
# Reliability index (RI):<br>RI < 0.3 – Not Reliable,<br>RI in range 0.3-0.5 – Borderline Reliability,<br>RI in range 0.5-0.75 – Moderate Reliability,<br>RI >= 0.75 – High Reliability
# Up to 5 most similar structures in the training set. The records include structure name, experimental value and similarity index. This index is based on QSAR analysis of logLD50 data. Similarity index varies from zero to unity. Only compounds with similarity index greater than 0.5 are presented.
# Click the tab to browse for similar structures from various administration types. If no similar structures are found, the tab is disabled.<br>
# Lipophilic parts of the molecule are highlighted in green, hydrophilic groups in red, and the intensity of the color indicates the predicted degree of lipophilicity or hydrophilicity of an atom or a substructure
# LogP predictions obtained using Two different LogP calculation algorithms (AB/LogP 2.0 and ACD/Labs) are provided. AB/Log 2.0 predictions are supplemented by the assessment of prediction reliability by the means of calculated Reliability Index value
# Up to 5 most similar drug-like structures with experimental parameters
# Up to 5 most similar drug-like structures with experimental parameters
'''Note:''' Prediction reliability classification according to Reliability Index (RI) values:
* RI < 0.3 – Not Reliable,
* RI in range 0.3-0.5 – Bordeline Reliability,
* RI in range 0.5-0.75 – Moderate Reliability,
* RI >= 0.75 – High Reliability
<br />
<br />


Line 68: Line 45:
[[Image:logp_consensus.png|center]]
[[Image:logp_consensus.png|center]]
<br />
<br />
# Species: rat, mouse.<br>Administration type: intraperitoneal, oral, intravenous, subcutaneous.
# ...
# Predicted LD50 in mg/kg
# Reliability index (RI):<br>RI < 0.3 – Not Reliable,<br>RI in range 0.3-0.5 – Borderline Reliability,<br>RI in range 0.5-0.75 – Moderate Reliability,<br>RI >= 0.75 – High Reliability
# Up to 5 most similar structures in the training set. The records include structure name, experimental value and similarity index. This index is based on QSAR analysis of logLD50 data. Similarity index varies from zero to unity. Only compounds with similarity index greater than 0.5 are presented.
# Click the tab to browse for similar structures from various administration types. If no similar structures are found, the tab is disabled.<br>
 
 
# Lipophilic parts of the molecule are highlighted in green, hydrophilic groups in red, and the intensity of the color indicates the predicted degree of lipophilicity or hydrophilicity of an atom or a substructure
# LogP predictions obtained using Two different LogP calculation algorithms (AB/LogP 2.0 and ACD/Labs) are provided. AB/Log 2.0 predictions are supplemented by the assessment of prediction reliability by the means of calculated Reliability Index value
# Up to 5 most similar drug-like structures with experimental parameters
# Up to 5 most similar drug-like structures with experimental parameters
'''Note:''' Prediction reliability classification according to Reliability Index (RI) values:
* RI < 0.3 – Not Reliable,
* RI in range 0.3-0.5 – Bordeline Reliability,
* RI in range 0.5-0.75 – Moderate Reliability,
* RI >= 0.75 – High Reliability
<br />
<br />


Revision as of 13:43, 18 May 2012

Overview


This module calculates the value of the octanol-water partition coefficient – LogP. Reliability of predictions is quantitatively estimated via the calculation of the Reliability Index value.

...

Features

  • Calculate the octanol-water partition coefficient for a wide range of neutral compounds under standard conditions, at 25°C
  • Calculations are provided with 95% confidence intervals, or reliability Index (RI)
  • Review bioconcentration factor (BCF) and the adsorption coefficient (Koc)
  • Evaluate Rule-of-5 compliance
  • Train the model with experimental values to improve predictions for proprietary chemical space


Interface


ACD/LogP Classic


File:acdlogp classic.png


  1. LogP prediction obtained using ACD/Labs LogP calculation algorithm.
  2. ...



ACD/LogP GALAS


File:acdlogp galas.png


  1. Lipophilic parts of the molecule are highlighted in green, hydrophilic groups in red, and the intensity of the color indicates the predicted degree of lipophilicity or hydrophilicity of an atom or a substructure.
  2. LogP prediction obtained using GALAS modeling methodology.
  3. Reliability index (RI):
    RI < 0.3 – Not Reliable,
    RI in range 0.3-0.5 – Borderline Reliability,
    RI in range 0.5-0.75 – Moderate Reliability,
    RI >= 0.75 – High Reliability
  4. Up to 5 most similar drug-like structures with experimental parameters



Consensus LogP


File:logp consensus.png


  1. ...
  2. Up to 5 most similar drug-like structures with experimental parameters



Technical information


LogP module provides the estimate of the value of the octanol-water partitioning coefficient for neutral species. Reliability of each prediction is quantitatively estimated via the calculation of the Reliability Index value. In addition a color-coded representation of the predicted property distribution is provided indicating lipophilic and hydrophilic parts of the compound structure.

Training set size: 11,387
Internal validation set size: 4,890
Main sources of experimental data:

  • Reference books:
    • The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals, O'Neil, M.J., Smith, A., Heckelman, P.E., Budavari, S., Eds. 13th Edition, Merck & Co., Inc., Whitehouse Station, NJ, 2001
    • Therapeutic Drugs, Dolery, C., Ed. 2nd Edition, Churchill Livingstone, New York, NY, 1999
    • Clarke's Isolation and Identification of Drugs, Moffat, A.C., Jackson, J.V., Moss, M.S., Widdop, B., Eds. 2nd Edition, The Pharmaceutical Press, London, 1986
  • Various articles from peer-reviewed scientific journals*
  • Other public data sources (online databases, handbooks, etc.)

* - Articles reporting LogP models by other authors were the predominant type among analyzed literature, meaning that each publication contained larger collections of experimental data (usually in the order of tens or hundreds compounds) compiled from corresponding original experimental articles.

Internal Validation


Table 1. ACD/LogP (AB/LogP v2.0) model performance statistics for the various fractions of the internal validation set.
Subset Coverage of the entire
internal validation set (N=4,890) 		R2 RMSE
RI > 0.3
N = 4,872
99.6%   
0.94 0.46
RI > 0.5
N = 4,772
97.6%   
0.95 0.44
RI > 0.75
N = 3,345
68.7%   
0.96 0.36
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