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Residue preference mapping of ligand fragments in the protein data bank

Wang, L and Xie, Z and Wipf, P and Xie, XQ (2011) Residue preference mapping of ligand fragments in the protein data bank. Journal of Chemical Information and Modeling, 51 (4). 807 - 815. ISSN 1549-9596

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Abstract

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. © 2011 American Chemical Society.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Wang, LLIW30@pitt.eduLIW30
Xie, Z
Wipf, Ppwipf@pitt.eduPWIPF
Xie, XQSean.Xie@pitt.eduXIX15
Date: 25 April 2011
Date Type: Publication
Journal or Publication Title: Journal of Chemical Information and Modeling
Volume: 51
Number: 4
Page Range: 807 - 815
DOI or Unique Handle: 10.1021/ci100386y
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Refereed: Yes
ISSN: 1549-9596
MeSH Headings: Algorithms; Binding Sites; Databases, Protein; Drug Design; Information Storage and Retrieval--methods; Ligands; Models, Molecular; Protein Binding; Protein Interaction Mapping--methods; Proteins--chemistry; Structure-Activity Relationship
Other ID: NLM NIHMS281798, NLM PMC3081969
PubMed Central ID: PMC3081969
PubMed ID: 21417260
Date Deposited: 28 May 2013 15:22
Last Modified: 13 Apr 2020 12:55
URI: http://d-scholarship-dev.library.pitt.edu/id/eprint/18745

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