Curation of Computational Chemical Libraries Demonstrated with Alpha-Amino Acids.

Exhaustive generation of molecular structures has numerous chemical and biochemical applications such as drug design, molecular database construction, exploration of alternative biochemistries, and many more. Mathematically speaking, these are graph generators with chemical constraints. In the field, the most efficient generator currently (MOLGEN) is a commercial product, limiting its use. Alternative to that, another molecular structure generator, MAYGEN, is a recent open-source tool with efficiency comparable to MOLGEN and the capacity for users to increase its performance by adding new features. One of the research fields that can benefit from this development is astrobiology; structure generators allow researchers to supplement experimental data with computational possibilities for alternative biochemistry. This protocol details one use case for structure generation in astrobiology, namely the generation and curation of alpha-amino acid libraries. Using open-source structure generators and cheminformatics tools, the practices described here can be implemented beyond astrobiology for the low-cost creation and curation of chemical structure libraries for any research question.

Surge: a fast open-source chemical graph generator.

Chemical structure generators are used in cheminformatics to produce or enumerate virtual molecules based on a set of boundary conditions. The result can then be tested for properties of interest, such as adherence to measured data or for their suitability as drugs. The starting point can be a potentially fuzzy set of fragments or a molecular formula. In the latter case, the generator produces the set of constitutional isomers of the given input formula. Here we present the novel constitutional isomer generator surge based on the canonical generation path method. Surge uses the nauty package to compute automorphism groups of graphs. We outline the working principles of surge and present benchmarking results which show that surge is currently the fastest structure generator. Surge is available under a liberal open-source license.

MAYGEN: an open-source chemical structure generator for constitutional isomers based on the orderly generation principle.

The generation of constitutional isomer chemical spaces has been a subject of cheminformatics since the early 1960s, with applications in structure elucidation and elsewhere. In order to perform such a generation efficiently, exhaustively and isomorphism-free, the structure generator needs to ensure the building of canonical graphs already during the generation step and not by subsequent filtering. Here we present MAYGEN, an open-source, pure-Java development of a constitutional isomer molecular generator. The principles of MAYGEN's architecture and algorithm are outlined and the software is benchmarked in single-threaded mode against the state-of-the-art, but closed-source solution MOLGEN, as well as against the best open-source solution PMG. Based on the benchmarking, MAYGEN is on average 47 times faster than PMG and on average three times slower than MOLGEN in performance.

Chemical graph generators.

Chemical graph generators are software packages to generate computer representations of chemical structures adhering to certain boundary conditions. Their development is a research topic of cheminformatics. Chemical graph generators are used in areas such as virtual library generation in drug design, in molecular design with specified properties, called inverse QSAR/QSPR, as well as in organic synthesis design, retrosynthesis or in systems for computer-assisted structure elucidation (CASE). CASE systems again have regained interest for the structure elucidation of unknowns in computational metabolomics, a current area of computational biology.

COCONUT online: Collection of Open Natural Products database.

Natural products (NPs) are small molecules produced by living organisms with potential applications in pharmacology and other industries as many of them are bioactive. This potential raised great interest in NP research around the world and in different application fields, therefore, over the years a multiplication of generalistic and thematic NP databases has been observed. However, there is, at this moment, no online resource regrouping all known NPs in just one place, which would greatly simplify NPs research and allow computational screening and other in silico applications. In this manuscript we present the online version of the COlleCtion of Open Natural prodUcTs (COCONUT): an aggregated dataset of elucidated and predicted NPs collected from open sources and a web interface to browse, search and easily and quickly download NPs. COCONUT web is freely available at https://coconut.naturalproducts.net .