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Substructure and whole molecule approaches for calculating log P.
R Mannhold1, H van de Waterbeemd
1Molecular Drug Research Group, Heinrich-Heine-Universiteit, Düsseldorf, Germany. Raimund.Mannhold@uni-duesseldorf.de
Journal of Computer-Aided Molecular Design
|May 15, 2001
Summary
Medicinal chemists calculate lipophilicity (log P) using substructure or whole molecule methods. This review compares these approaches, discussing their strengths and weaknesses for predicting drug properties.
Area of Science:
- Medicinal Chemistry
- Computational Chemistry
- Drug Discovery
Background:
- Lipophilicity, quantified by the partition coefficient (log P), is crucial for drug pharmacokinetics and pharmacodynamics.
- Accurate prediction of log P from molecular structure is a key challenge in drug design.
Purpose of the Study:
- To review and compare methods for calculating lipophilicity (log P) from molecular structure.
- To discuss the advantages and disadvantages of different computational approaches.
- To propose a classification scheme for log P calculation methods.
Main Methods:
- Overview of substructure approaches (atom contribution and fragmental methods).
- Description of whole molecule approaches (e.g., molecular lipophilicity potentials, topological indices).
- Comparative analysis of the predictive power of various calculation methods.
Main Results:
- Substructure methods rely on summing contributions from molecular fragments.
- Whole molecule methods analyze the entire molecular structure.
- The review highlights the trade-offs between different computational strategies for log P prediction.
Conclusions:
- Both substructure and whole molecule methods offer valuable tools for estimating lipophilicity.
- Understanding the strengths and limitations of each approach is essential for effective drug design.
- A proposed classification scheme aids in selecting appropriate log P calculation methods.