title: Biomacromolecular quantitative structure-activity relationship (BioQSAR): a proof-of-concept study on the modeling, prediction and interpretation of protein-protein binding affinity.
abstract: Quantitative structure-activity relationship (QSAR), a regression modeling methodology that establishes statistical correlation between structure feature and apparent behavior for a series of congeneric molecules quantitatively, has been widely used to evaluate the activity, toxicity and property of various small-molecule compounds such as drugs, toxicants and surfactants. However, it is surprising to see that such useful technique has only very limited applications to biomacromolecules, albeit the solved 3D atom-resolution structures of proteins, nucleic acids and their complexes have accumulated rapidly in past decades. Here, we present a proof-of-concept paradigm for the modeling, prediction and interpretation of the binding affinity of 144 sequence-nonredundant, structure-available and affinity-known protein complexes (Kastritis et al. Protein Sci 20:482-491, 2011) using a biomacromolecular QSAR (BioQSAR) scheme. We demonstrate that the modeling performance and predictive power of BioQSAR are comparable to or even better than that of traditional knowledge-based strategies, mechanism-type methods and empirical scoring algorithms, while BioQSAR possesses certain additional features compared to the traditional methods, such as adaptability, interpretability, deep-validation and high-efficiency. The BioQSAR scheme could be readily modified to infer the biological behavior and functions of other biomacromolecules, if their X-ray crystal structures, NMR conformation assemblies or computationally modeled structures are available.
authors.affiliation: Center of Bioinformatics-COBI, School of Life Science and Technology, University of Electronic Science and Technology of China-UESTC, Chengdu 610054, China. p_zhou@uestc.edu.cn
authors.forename: Peng
authors.initials: P
authors.lastname: Zhou
authors.forename: Congcong
authors.initials: C
authors.lastname: Wang
authors.forename: Feifei
authors.initials: F
authors.lastname: Tian
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Ren
authors.forename: Chao
authors.initials: C
authors.lastname: Yang
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
mesh_terms: D000465:Algorithms; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D012044:Regression Analysis; D055672:Static Electricity