Calculator Plugins : logP Plugin

This manual gives you a walk-through on how to use the logP Plugin:

Introduction

 

The logP Plugin calculates the octanol/water partition coefficient, which is used in QSAR analysis and rational drug design as a measure of molecular hydrophobicity. The calculation method is based on the publication of Viswanadhan et al. The logP of a molecule is composed of the increment of its atoms. However, the algorithm described in the paper was modified at several points:

  1. Many atomic types were redefined to accommodate electron delocalization and contributions of ionic forms were added. 
  2. The logP of zwitterions are calculated from their logD value at their isoelectric point. 
  3. The effect of hydrogen bonds on logP is considered if there is a chance to form a six membered ring between suitable donor and acceptor atoms. 
  4. New atom types were introduced especially for sulfur, carbon, nitrogen and metal atoms. 

To find details on logP calculation, see the following page. 

The result of the calculation appears in a new window, either in a MarvinView (for a 2D view) window or in a MarvinSpace (for a 3D view) window.
 

Fig. 1 LogP result window with atomic increments displayed in MarvinView

 


Fig. 2 LogP result window with atomic increments displayed in MarvinSpace

 

Options
 

General Options

 

Different general options can be set in the logP Options window:

  • Method
    • VG: the calculation method derived from Viswanadhan et al. is applied.
    • KLOP: logP data from Klopman et al. is applied.
    • PHYSPROP: logP data from PHYSPROP© database is used.
    • User defined: if a training set of structures and corresponding experimental logP values is available, it can be used as a database for logP calculations. 
      See the manual page on creating such training sets.
    • Weighted: default setting. The use of methods can be combined by the user. Selecting this method turns the Method weights section active.
  • Training ID: if the User defined or the Weighted method is selected, this dropdown list becomes active. All created training sets are listed here. Choose the one to apply for the calculation. 
  • Method weights: you can set the weights of the methods used in the calculations. Acitve only if Weighted method is selected.
  • Electrolyte concentration
    • Cl- concentration: can be set between 0.1 and 0.25 mol/L.
    • Na+ K+ concentration: can be set between 0.1 and 0.25 mol/L.
  • Take major tautomeric form: the logP of the major tautomer will be calcutated.
     

Fig. 3 logP Options window with the General Options panel

 

On logP calculation methods

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The logP prediction methods were developed partly based on the atom types given in Viswanadhan et al. The three abbrevations only refer to the appropiate training logP data set according to the references. The weighted method is a combination of the above three logP calclulations, in which case the values given by the three methods are equally weighted by the default setting. The calculated logP in this way will be the arithmetic average of the three methods. The weighted method usually provides more reliable logP values than any one of the three separate methods.

 

Display Options

 

Different display options can be set in the logP Options window:

  • Decimal places: setting the number of decimal places with which the result value is given.
  • Show value
    • Increments: calculates and shows the increments for atoms one by one.
    • logP : shows the value of logP
  • Display in MarvinSpace: the result window opens as 3D MarvinSpace viewer. If unchecked, the results will be shown in a 2D MarvinView panel.

 

Fig. 4 logP Options window with the Display Options panel

References

  1. Viswanadhan, V. N.; Ghose, A. K.; Revankar, G. R.; Robins, R. K., J. Chem. Inf. Comput. Sci., 1989, 29, 163-172; doi
  2. Klopman, G.; Li, Ju-Yun.; Wang, S.; Dimayuga, M.: J.Chem.Inf.Comput.Sci., 1994, 34, 752; doi
  3. PHYSPROP© database
  4. Csizmadia, F; Tsantili-Kakoulidou, A.; Pander, I.; Darvas, F., J. Pharm. Sci., 1997, 86, 865-871; doi