Frequently Asked Questions

1. Super Natural II

1.1 Super Natural II

Super Natural II is a database for natural products. The first version of the database known as Super Natural, was designed in the year 2006 with almost 46000 natural compounds, together with corresponding vendor vendors information.

1.2 Purpose of Super Natural II

Super Natural II provides a highly curated online database for natural products. This database contains 325,508 natural products extracted from various resources. Super Natural II offers additional search and analysis options. It also provides the toxicity prediction for the database compounds. For instance, a substructure search can be performed to identify compounds containing this substructure. Additionally, possible target proteins and pathways are predicted for the natural compounds, based on 2D structural similarity search to known drug molecules.
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2. System Requirements

System Requirements

Super Natural II data is stored in a relational MySQL database. To handle the chemical information within the database, the MyChem package is used. MyChem relies for most of its functions on the Open Babel toolbox. The website is built using PHP; web access is enabled via Apache HTTP Server. We recommend a recent version of Mozilla Firefox; Google Chrome, Microsoft Internet Explorer and Apple Safari were tested with some configurations. JavaScript has to be enabled; Java is required to use all features of the site.
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3. Biological Background

3.1 What are natural compounds?

Natural products are molecules synthesized by living organisms. The chemical diversity of these natural compounds is tremendous and offers inspiration for innovations in medicine, nutrition, agrochemical research and life sciences. Most of the currently used cosmetics and drugs are base on natural products.

3.2 How are natural compounds classified?

Naturally occuring compounds can be broadly classified into three categories. First,compounds which are produced in most cells and play important roles in the metabolism and reproductions of those cells. They are often called primary metabolites including nucleic acids, amino acids and sugars. Secondly, macro molecular polymeric materials such as cellulose, lignins and proteins. Finally, secondary metabolites including classes like polyketides and fatty acids, terpenoids and steroids, phenylpropanoids, alkaloids, specialized amino acids, peptides and carbohydrates.
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4. Website

4.1 Usage of the Website

The website provides insight into a huge database of natural products, which are collected from different sources. There are three main search buttons; compounds, templates and mechanism of action (MoA). The compounds button allows to search for natural products based on compound name, supplier ID or classifications.

4.2 What are Molecular fingerprints?

Molecular fingerprints represent certain structural features of a molecule. There are two processes fingerprints are primarily used for:
similarity measures like calculations and screenings. Whereas calculation is a quantify of similarity of two molecules. However screening is a way of eliminating molecules as candidates in a substructure search. The fingerprint algorithm examines the molecule and generates patterns of the atom. The output is a string of bits and is added to the fingerprint.

4.3 What is the Tanimoto coefficient?

For similarity screening of a compound against Super Natural II database fingerprints of both molecules are used. Fragments of the molecules are assigned to set bits in the 1024 bit vector concatenated (FP2, FP4) Open Babel fingerprint. To compare the similarity between the compounds the Tanimoto coefficient is applied.

The tanimoto coefficient uses the bits set to one in both fingerprints. AB is the number of bits set to one in both molecules. A is the number of bits set to one in molecule A and B is the number of bits set to one in molecule B.
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4.4 Compound search

4.4.1 Compound name

Using compound search one can search natural products via compound name (red), physico-chemical properties (blue) tox-class (orange) or classification (yellow). It is all possible to filter only those compounds which are purchaseable (green) The figure below, shows a search with the compound name Curcumin. If a searched compound is available by more than one supplier, all the suppliers are listed.

In the result page (second picture) compounds properties are displayed (red), vendors information (blue). It is possible to click compound cluster tab (green) to see a heat map of similar compounds. Similarity search (pink) and pathway information (orange) can be obtain too.

4.4.2 Search_criteria

The search via Supplier/ID allows you to search in all natural compounds available in Super Natural II. Simple search simple criteria like the ID or the name of the supplier can be used as well as advancerd criteria like the number of chiral centers or logp. With this type of search you can find similar structures.

4.4.3 CAS numbers

CAS Registry Numbers are unique numerical identifiers assigned by the Chemical Abstracts Service to every chemical described in the open scientific literature. You can search for any specific CAS number.

4.4.4 Classification

Here you can search natural compounds based on their individual class.
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4.5 Template search

4.5.1 How to search for a compound using a defined template ?

The Template Search allows you to sift through the database based on a small assortment of substructures. Only substructures are available, which can be found in the database are offered. At most 450 hits per substructure are shown. There are templates for amino acids, alpha sugars,beta sugars, D-sugars, aromatic rings, bases, bicyclic rings, fused rings, rings and plolycyclic compounds. In the figure above, a simple template search for alpha sugars (red) as template results in 63 hits.
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4.6 Customised compound search

4.6.1 Search via self designed compounds

Here you can search compounds based on self-designed template.
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4.7 Mechanism of action prediction

4.7.1 Via molecule search

Here one can get information regarding the target protein. Users can specify a desired template (orange) for a 2D similarity based search for similar molecules.

4.7.2 Via target search

The target search can be used to find valid compounds for a target, which is specified by name or Uniprot ID (red). Similar Compounds are displayed (blue) with Tanimoto scores. By clicking the desired compound, further information on different targets (blue, orange) with respect to known compounds (yellow) and similar natural compounds (green) can be obtained.
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4.8Pathways prediction via KEGG

Here one can get information about the biochemical pathways associated with the compounds. The input is organism and pathway as highlighted in pink and green in the above example. The compounds specific to the input are shown as output. The pathways information is shown on a new page (blue) and the compounds are also shown (yellow). Mouseover a compound pops up the result with reference compounds and similarity value (red). StructuresSure are also shown.
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4.9 Toxicity prediction via ProTox

ProTox is the first freely available web server for toxicity prediction method based on chemical similarity and the identification of toxic fragments and demonstrates good performance in comparison to available QSAR-based methods. ProTox prediccts the median oral lethal doses (LD50 values) and toxicity classes in rodents. In addition to the oral toxicity prediction, the web server indicates possible toxicity targets based on a collection of protein-ligand-based pharmacophores ('toxicophores') and therefore provides suggestions for the mechanism of toxicity development. Super Natural II provides possible toxicity alert for the use of a particular natural compound. However, the absence of such toxicity prediction or alert for a compound should not be taken as an indication of safety.
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4.10 Clusters

Cluster analysis of the entire dataset of natural compounds reveals the corresponding diversity. Each cluster gives information about related to compounds in an interactive heatmap view. The red color corresponds to high similarity and fading colors to lower similarity.

The compound name, SN_ID, IUPAC and SMILES can be used to locate the cluster of the molecule (as shown in the above picture). Moving the mouse on the heatmap will pop up the molecule and the corresponding similar molecule. The two compounds structure are highlighted in blue and green, respectively.
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