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Journal of Computer-Aided Molecular Design

, Volume 8, Issue 3, pp 243–256 | Cite as

The development of a simple empirical scoring function to estimate the binding constant for a protein-ligand complex of known three-dimensional structure

  • Hans-Joachim Böhm
Research Papers

Summary

A new simple empirical function has been developed that estimates the free energy of binding for a given protein-ligand complex of known 3D structure. The function takes into account hydrogen bonds, ionic interactions, the lipophilic protein-ligand contact surface and the number of rotatable bonds in the ligand. The dataset for the calibration of the function consists of 45 protein-ligand complexes. The new energy function reproduces the binding constants (ranging from 2.5·10-2 to 4·10-14 M, corresponding to binding energies between -9 and -76 kJ/mol) of the dataset with a standard deviation of 7.9 kJ/mol, corresponding to 1.4 orders of magnitude in binding affinity. The individual contributions to protein-ligand binding obtained from the scoring function are: ideal neutral hydrogen bond: -4.7 kJ/mol; ideal ionic interaction: -8.3 kJ/mol; lipophilic contact: -0.17 kJ/mol Å2; one rotatable bond in the ligand: +1.4 kJ/mol. The function also contains a constant contribution (+5.4 kJ/mol) which may be rationalized as loss of translational and rotational entropy. The function can be evaluated very fast and is therefore also suitable for application in a 3D database search or de novo ligand design program such as LUDI.

Key words

Proteins Protein-ligand interaction De novo design Scoring function 

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Copyright information

© ESCOM Science Publishers B.V 1994

Authors and Affiliations

  • Hans-Joachim Böhm
    • 1
  1. 1.Central ResearchBASF AGLudwigshafenGermany

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