Abstract
We have developed PLASS (Protein-Ligand Affinity Statistical Score), a pair-wise potential of mean-force for rapid estimation of the binding affinity of a ligand molecule to a protein active site. This scoring function is derived from the frequency of occurrence of atom-type pairs in crystallographic complexes taken from the Protein Data Bank (PDB). Statistical distributions are converted into distance-dependent contributions to the Gibbs free interaction energy for 10 atomic types using the Boltzmann hypothesis, with only one adjustable parameter. For a representative set of 72 protein-ligand structures, PLASS scores correlate well with the experimentally measured dissociation constants: a correlation coefficient R of 0.82 and RMS error of 2.0 kcal/mol. Such high accuracy results from our novel treatment of the volume correction term, which takes into account the inhomogeneous properties of the protein-ligand complexes. PLASS is able to rank reliably the affinity of complexes which have as much diversity as in the PDB.
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Ozrin, V., Subbotin, M. & Nikitin, S. PLASS: Protein-ligand affinity statistical score – a knowledge-based force-field model of interaction derived from the PDB. J Comput Aided Mol Des 18, 261–270 (2004). https://doi.org/10.1023/B:JCAM.0000046819.20241.16
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DOI: https://doi.org/10.1023/B:JCAM.0000046819.20241.16