Ay uncover common principles of compoundprotein encounters. The study of compound-protein interactions has been in the core of drug development programs for decades. As high specificity of protein target binding is regarded as desirable for the therapeutic success, the elements influencing binding specificity of drug compounds have already been investigated intensively, and their continued study remains a central investigation objective in each academia and pharmaceutical market. Since it may well cause adverse side effects, promiscuous binding of drugs to numerous off-target (R)-Propranolol custom synthesis proteins is of particular concern (Lounkine et al., 2012; Hu and Bajorath, 2013; Rudmann, 2013; Hu et al., 2014). Experimental too as computational research have generated a wealth of Cinnabarinic acid supplier expertise on the rules that govern the association of physicochemical properties of drug compounds and their target protein spectrum (Tarcsay and Keser , 2013). On the other hand, u unexpected binding to off-targets could also help to position established drugs for novel medicinal indications (for review of good and unfavorable effects of promiscuity see Peters, 2013). To probe for promiscuity and also other ADME (absorption, distribution, metabolism, and excretion) properties, appropriate representative protein panels have already been established, with which compound promiscuity is often assayed experimentally (Krejsa et al., 2003). Simply because detailed computational allagainst-all docking studies proved prohibitive (for lack of structural facts or limiting computational power), such experimental binding surveys happen to be analyzed to establish general guidelines that associate physicochemical properties of compounds with binding promiscuity of drugs. One example is, it was discovered that lipophilicity (logP) and standard character (pKa ) appear positively correlated with promiscuous binding behavior (Tarcsay and Keser , 2013). u In this study, we performed a systematic analysis of metabolite-protein interactions and compared them with the traits of drug-protein binding events. We based our analysis on observed interactions of modest compounds with proteins within the PDB as has been accomplished for drugs (Haupt et al., 2013) and drug-like compounds (Sturm et al., 2012) before. Here, we extended the analysis to incorporate naturally occurring metabolites and to reveal doable similarities and differences between the two compound sets with regard to protein binding behavior thereby examining the transferability of approaches, algorithmic ideas, and physiochemical principles from theFrontiers in Molecular Biosciences | www.frontiersin.orgSeptember 2015 | Volume two | ArticleKorkuc and WaltherCompound-protein interactionsrich drug development field towards the realm of metabolomics. A big variety of physicochemical properties was profiled and their influence around the binding characteristics investigated. In specific, we assessed the degree of specificitypromiscuity of compounds with respect to their underlying chemical structure. We studied promiscuity from the perspective of compoundbased also as protein-target-based properties applying both descriptive and predictive statistical approaches. A plethora of studies has been devoted to the computational evaluation and prediction of compound-protein interactions. However, given their pharmacological relevance, such studies have mainly focused on drug-protein interactions (Carbonell and Faulon, 2010; Yabuuchi et al., 2011; Yu and Wild, 2012; Haupt et al., 2013; Ding et al., 2014). Computational st.
