ZINC 15 – Ligand Discovery for Everyone

Abstract

Many questions about the biological activity and availability of small molecules remain inaccessible to investigators who could most benefit from their answers. To narrow the gap between chemoinformatics and biology, we have developed a suite of ligand annotation, purchasability, target, and biology association tools, incorporated into ZINC and meant for investigators who are not computer specialists. The new version contains over 120 million purchasable “drug-like” compounds – effectively all organic molecules that are for sale – a quarter of which are available for immediate delivery. ZINC connects purchasable compounds to high-value ones such as metabolites, drugs, natural products, and annotated compounds from the literature. Compounds may be accessed by the genes for which they are annotated as well as the major and minor target classes to which those genes belong. It offers new analysis tools that are easy for nonspecialists yet with few limitations for experts. ZINC retains its original 3D roots – all molecules are available in biologically relevant, ready-to-dock formats. ZINC is freely available at .

Existing drugs as broad-spectrum and potent inhibitors for Zika virus by targeting NS2B-NS3 interaction

“…The 3D structures for niclosamide, nitazoxanide, and temoporfin were downloaded in SDF format from the ZINC15 library [74]. The NS2B-bound crystal structures of the Dengue NS3 protease (PDB ID: 3U1I [43]) and of the Zika NS3 protease (PDB ID: 5LC0 [44]) were used as docking targets to predict the possible bound conformations of these compounds.…”

<em>In Silico</em> Screening and Analysis of Potential Inhibitors of Arylamine N-Acetyltransferases (NATs) from the Traditional Chinese Medicine: A Study Using Free Available Tools

“…Vina [33] implemented in the MTiOpenSreen [28] web server. Each compound is identified according to the registration number in the ZINC15 [27] database.…”

“…The library containing 36,043 compounds from the Traditional Chinese Medicine (TCM) was downloaded in the SDF (Structures Data File) format from the ZINC database [27], catalog TCM Database@Taiwan [45]. Before the use, the TCM library was previously formatted and cleaned (to remove inorganics, large compounds, mixtures, empty structures, salts and duplicates) with Bank…”

“…There is currently a wide range of free resources [23][24][25][26][27][28] and free software packages [29][30][31][32][33][34][35] dedicated to drug discovery and design. The availability of free resources and tools allows scientists from all over the world, independent of the financial support, to plan and test hypotheses through in silico experiments.…”

Extending accessible chemical space for the identification of novel leads

“…Moreover, the lead-like potential of highly diverse compounds of mostly limited chemical complexity (different from, for example, natural product-derived molecules) will need to be carefully evaluated. In this context, it should also be noted that according to a recent proposal, more than 120 million drug-like compounds might currently be purchasable worldwide [26]. Evaluating anywhere close to such numbers of already synthesized compounds in conventional screens will present formidable challenges in drug discovery.…”