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FGDB: a comprehensive graph database of ligand fragments from the Protein Data Bank.

ABSTRACT: This work presents Fragment Graph DataBase (FGDB), a graph database of ligand fragments extracted and generated from the protein entries available in the Protein Data Bank (PDB). FGDB is meant to support and elicit campaigns of fragment-based drug design, by enabling users to query it in order to construct ad hoc, target-specific libraries. In this regard, the database features more than 17 000 fragments, typically small, highly soluble and chemically stable molecules expressed via their canonical Simplified Molecular Input Line Entry System (SMILES) representation. For these fragments, the database provides information related to their contact frequencies with the amino acids, the ligands they are contained in and the proteins the latter bind to. The graph database can be queried via standard web forms and textual searches by a number of identifiers (SMILES, ligand and protein PDB ids) as well as via graphical queries that can be performed against the graph itself, providing users with an intuitive and effective view upon the underlying biological entities. Further search mechanisms via advanced conjunctive/disjunctive/negated textual queries are also possible, in order to allow scientists to look for specific relationships and export their results for further studies. This work also presents two sample use cases where maternal embryonic leucine zipper kinase and mesotrypsin are used as a target, being proteins of high biomedical relevance for the development of cancer therapies. Database URL: http://biochimica3.bio.uniroma3.it/fragments-web/.

SUBMITTER: Toti D

PROVIDER: S-EPMC9239314 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Residue preference mapping of ligand fragments in the Protein Data Bank.

Project description:The interaction between small molecules and proteins is one of the major concerns for structure-based drug design because the principles of protein-ligand interactions and molecular recognition are not thoroughly understood. Fortunately, the analysis of protein-ligand complexes in the Protein Data Bank (PDB) enables unprecedented possibilities for new insights. Herein, we applied molecule-fragmentation algorithms to split the ligands extracted from PDB crystal structures into small fragments. Subsequently, we have developed a ligand fragment and residue preference mapping (LigFrag-RPM) algorithm to map the profiles of the interactions between these fragments and the 20 proteinogenic amino acid residues. A total of 4032 fragments were generated from 71?798 PDB ligands by a ring cleavage (RC) algorithm. Among these ligand fragments, 315 unique fragments were characterized with the corresponding fragment-residue interaction profiles by counting residues close to these fragments. The interaction profiles revealed that these fragments have specific preferences for certain types of residues. The applications of these interaction profiles were also explored and evaluated in case studies, showing great potential for the study of protein-ligand interactions and drug design. Our studies demonstrated that the fragment-residue interaction profiles generated from the PDB ligand fragments can be used to detect whether these fragments are in their favorable or unfavorable environments. The algorithm for a ligand fragment and residue preference mapping (LigFrag-RPM) developed here also has the potential to guide lead chemistry modifications as well as binding residues predictions.

| S-EPMC3081969 | biostudies-literature

SuperLigands - a database of ligand structures derived from the Protein Data Bank.

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| S-EPMC1173082 | biostudies-literature

Accurate Representation of Protein-Ligand Structural Diversity in the Protein Data Bank (PDB).

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iPfam: a database of protein family and domain interactions found in the Protein Data Bank.

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| S-EPMC3965099 | biostudies-literature

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| S-EPMC2413245 | biostudies-literature

PDBj Mine: design and implementation of relational database interface for Protein Data Bank Japan.

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| S-EPMC2997606 | biostudies-literature

A comprehensive database of verified experimental data on protein folding kinetics.

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Ligand-centered assessment of SARS-CoV-2 drug target models in the Protein Data Bank.

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