An unexpected way forward: towards a more accurate and rigorous protein-protein binding affinity scoring function by eliminating terms from an already simple scoring function. Issue 1 (2nd January 2018)

• Record Type: Journal Article
• Authors: Swanson, Jon; Audie, Joseph
• Is Part Of: Journal of biomolecular structure & dynamics. Volume 36:Issue 1(2018)
• Page Start: 83
• Page End: 97
• Publication Date: 2018-01-02
• Subjects: protein–protein interaction -- molecular modeling -- molecular recognition -- structural informatics -- biophysical chemistry; Biomolecules -- Periodicals; Molecular structure -- Periodicals; Molecular Biology -- Periodicals; Biomechanics -- Periodicals; 572
• DOI: 10.1080/07391102.2016.1268974
• Languages: English
• ISSNs: 0739-1102

Abstract

Abstract : A fundamental and unsolved problem in biophysical chemistry is the development of a computationally simple, physically intuitive, and generally applicable method for accurately predicting and physically explaining protein–protein binding affinities from protein–protein interaction (PPI) complex coordinates. Here, we propose that the simplification of a previously described six-term PPI scoring function to a four term function results in a simple expression of all physically and statistically meaningful terms that can be used to accurately predict and explain binding affinities for a well-defined subset of PPIs that are characterized by (1) crystallographic coordinates, (2) rigid-body association, (3) normal interface size, and hydrophobicity and hydrophilicity, and (4) high quality experimental binding affinity measurements. We further propose that the four-term scoring function could be regarded as a core expression for future development into a more general PPI scoring function. Our work has clear implications for PPI modeling and structure-based drug design.