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

@article{Bhm1994TheDO,
  title={The development of a simple empirical scoring function to estimate the binding constant for a protein-ligand complex of known three-dimensional structure},
  author={Hans-Joachim B{\"o}hm},
  journal={Journal of Computer-Aided Molecular Design},
  year={1994},
  volume={8},
  pages={243-256}
}
  • H. Böhm
  • Published 1 June 1994
  • Chemistry, Biology
  • Journal of Computer-Aided Molecular Design
SummaryA 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… 

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References

SHOWING 1-10 OF 68 REFERENCES

Functional group contributions to drug-receptor interactions.

The binding constants and structural components of 200 drugs and enzyme inhibitors have been used to calculate the average binding energies of 10 common functional groups. As expected, charged groups

Definition and display of steric, hydrophobic, and hydrogen-bonding properties of ligand binding sites in proteins using Lee and Richards accessible surface: validation of a high-resolution graphical tool for drug design.

The ability of the surface to accurately display steric complementarity between ligands and proteins was optimized using data from small molecule crystal structures and the possibility of displaying the chemical specificity of the binding site was investigated.

New hydrogen-bond potentials for use in determining energetically favorable binding sites on molecules of known structure.

An empirical energy function designed to calculate the interaction energy of a chemical probe group with a target molecule has been developed and the shape of some of the energy functions is demonstrated on molecules of pharmacological interest.

Toward the semiquantitative estimation of binding constants guides for peptide peptide binding in aqueous solution

Extension of the approach will allow, in those cases where there is good complementarity between ligand and receptor, the prediction of approximate peptide-peptide binding constants in aqueous solution.

A method for fast energy estimation and visualization of protein-ligand interaction

It becomes easier to find a roughly stable geometry of ligand molecules, and one can therefore make a rapid survey of the binding capability of many drug candidates through a new computational and graphical method for facilitating ligand-protein docking studies.

Toward an estimation of binding constants in aqueous solution: studies of associations of vancomycin group antibiotics.

The phenomenon of entropy/enthalpy compensation is considered, with the conclusion that enthalpic barriers to dissociations will result in larger losses in translational and rotational entropy in the association step.

Calculation of the free energy of association for protein complexes

  • N. HortonM. Lewis
  • Chemistry
    Protein science : a publication of the Protein Society
  • 1992
A method for calculating the association energy of quaternary complexes starting from their atomic coordinates is developed and it is shown that the calculated association can be used as a predictive tool for analyzing modeled molecular complexes.

Automated docking with grid‐based energy evaluation

The ability to generate feasible binding orientations of a small molecule within a site of known structure is important for ligand design. We present a method that combines a rapid, geometric docking

Extracting hydrophobic free energies from experimental data: relationship to protein folding and theoretical models.

It is shown here how the ideal gas equations, combined with experimental molar volumes, can account for changes in volume entropy and the increased strength of the hydrophobic interaction has implications for the energetics of protein folding, substrate binding, and nucleic acid base stacking and the interpretation of computer simulations.

Computer design of bioactive molecules: A method for receptor‐based de novo ligand design

The methodology presented employs a large template set of amino acid conformations which are iteratively pieced together in a model of the target receptor, and has proven useful as a precise model‐builder and has also shown the ability to design bioactive ligands.
...