How to use

I. Keyword search

NLDB provides a flexible keyword search function, enabling users to retrieve the structures of particular protein-ligand interactions in enzymatic reactions of interest. Various types of keywords are allowed in the search function, such as PDB entry ID, molecule name, organism, ligand name, KEGG reaction ID, EC number, UniProt accession number, chemical component ID and so on, as well as combinations of these keywords. According to the search keywords inputted in the search box of the NLDB top page, the following three results pages will be provided:

Output-1

A list of reactions with the data counts of three types of complexes, natural, analog, and ab initio (see About). (for example, Hexokinase, homo sapiens)

1. Natural?complexes, which are experimentally determined protein-ligand complex structures in PDB
2. Analog?complexes, which are?predicted based on known protein structures in a complex with a similar ligand (analog)
3. Ab initio?complexes, which are?predicted by docking a ligand to predicted or high confidence ligand-binding sites of a protein

When the input keywords include a KEGG reaction ID or when only a KEGG reaction is inputted, then the next output-2 page will be directly accessed. Otherwise, when you click the NL icon of the specific reactions ID, for example, R00796 (in the row surrounded by a red square), the output-2 will be displayed.

Output-2

A list of available complex structures for a particular enzymatic reaction of interest (see example)

The data counts of protein structures binding to a specific ligand, reactant or product in each complex type are shown in the top table, and the lists of different types of complex structures are also shown, in different tables. In addition, the binding affinities for each analog and ab initio complex structure are shown in the table.

Please select and click the NL icon of the specific structure, for example, 1dgk (chain N) to which ADP-921 originally bind (in the row surrounded by a red square), then the next output-3 page will be displayed.

Output-3

The detailed information of a specific protein-ligand complex structure (see example)

On this page, a list of interacting residues within 5.0A from the ligand atoms is shown in the ‘Interaction Residues’ table, and the complex structure is also visually displayed in the Jmol panel, in the top left-hand corner. Only for human proteins, variants including human polymorphisms and disease-associated mutations are shown in the ‘Variants’ table, and are highlighted if there are variants in the binding site of the protein.

Other detailed information about the reaction, the molecule, and the ligand chemical components is also shown and linked to the external databases, such as KEGG, PDBj and UniProt.

II. Enrichment analysis

NLDB provides an enrichment analysis of a set of KEGG compounds. This function enables users to retrieve enriched KEGG pathways with expected p-values.

In addition, a list of the reactions in each enriched pathway is also shown, in the same table format as that in the first result page of the keyword search.