Journal article
Halogenated ligands and their interactions with amino acids: Implications for structure–activity and structure–toxicity relationships
Journal of molecular graphics & modelling, Vol.27(2)
2008
PMID: 18524655
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The properties of chemicals are rooted in their molecular structure. It follows that structural analysis of specific interactions between ligands and biomolecules at the molecular level is invaluable for defining structure–activity relationships (SARs) and structure–toxicity relationships (STRs). This study has elucidated the structural and molecular basis of interactions of biomolecules with alkyl and aryl halides that are extensively used as components in many commercial pesticides, disinfectants, and drugs. We analyzed the protein structures deposited in Protein Data Bank (PDB) for structural information associated with interactions between halogenated ligands and proteins. This analysis revealed distinct patterns with respect to the nature and structural characteristics of halogen interactions with specific types of atoms and groups in proteins. Fluorine had the highest propensity of interactions for glycine, while chlorine for leucine, bromine for arginine, and iodine for lysine. Chlorine, bromine and iodine had the lowest propensity of interactions for cysteine, while fluorine had a lowest propensity for proline. These trends for highest propensity shifted towards the hydrophobic residues for all the halogens when only interactions with the side chain were considered. Halogens had equal propensities of interaction for the halogen bonding partners (nitrogen and oxygen atoms), albeit with different geometries. The optimal angle for interactions with halogens was ∼120° for oxygen atoms, and ∼96° for nitrogen atoms. The distance distributions of halogens with various amino acids were mostly bimodal, and the angle distributions were unimodal. Insights gained from this study have implications for the rational design of safer drugs and commercially important chemicals.
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Details
- Title
- Halogenated ligands and their interactions with amino acids: Implications for structure–activity and structure–toxicity relationships
- Creators
- Sandhya Kortagere - Department of Pharmacology and Environmental Bioinformatics & Computational Toxicology Center (ebCTC), University of Medicine & Dentistry of New Jersey (UMDNJ)-Robert Wood Johnson Medical School, 675 Hoes lane, Piscataway, NJ 08854, USASean Ekins - Department of Pharmacology and Environmental Bioinformatics & Computational Toxicology Center (ebCTC), University of Medicine & Dentistry of New Jersey (UMDNJ)-Robert Wood Johnson Medical School, 675 Hoes lane, Piscataway, NJ 08854, USAWilliam J Welsh - Department of Pharmacology and Environmental Bioinformatics & Computational Toxicology Center (ebCTC), University of Medicine & Dentistry of New Jersey (UMDNJ)-Robert Wood Johnson Medical School, 675 Hoes lane, Piscataway, NJ 08854, USA
- Publication Details
- Journal of molecular graphics & modelling, Vol.27(2)
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Identifiers
- 991014877874404721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemical Research Methods
- Biochemistry & Molecular Biology
- Computer Science, Interdisciplinary Applications
- Crystallography
- Mathematical & Computational Biology