ISSN:
1573-4951
Keywords:
Binding affinity prediction
;
Empirical scoring function
;
De novo molecular design
;
Protein–ligand complexes
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract This paper describes the development of a simple empirical scoringfunction designed to estimate the free energy of binding for aprotein–ligand complex when the 3D structure of the complex is knownor can be approximated. The function uses simple contact terms to estimatelipophilic and metal–ligand binding contributions, a simple explicitform for hydrogen bonds and a term which penalises flexibility. Thecoefficients of each term are obtained using a regression based on 82ligand–receptor complexes for which the binding affinity is known. Thefunction reproduces the binding affinity of the complexes with across-validated error of 8.68 kJ/mol. Tests on internal consistency indicatethat the coefficients obtained are stable to changes in the composition ofthe training set. The function is also tested on two test sets containing afurther 20 and 10 complexes, respectively. The deficiencies of this type offunction are discussed and it is compared to approaches by other workers.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1007996124545
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