Hydrogen bond energy-based comparative analysis of protein-ligand interactions and similarity assessment of protein-DNA complex models

1 online resource (127 pages) : PDF

2022

University of North Carolina at Charlotte

Hydrogen bonds play a vital role in protein-DNA interactions. In particular, side chain-base hydrogen bonds are crucial to the binding specificity between protein and DNA. Mutations effecting interface hydrogen bonds in protein-DNA complexes have been linked to changes in binding specificity and are implicated in various diseases. However, knowledge about the distribution of hydrogen bond energy (HBE) in protein-DNA complexes as compared to other important biomolecular complexes is unknown. Here, we performed a systematic comparative analysis of hydrogen bond energy (HBE) in three protein-ligand complexes; protein-DNA, protein-protein and protein-peptide. Our results show that while the hydrogen bonds in protein-protein and protein-peptide complexes are predominantly strong, a unique, almost equal distribution of strong and weak hydrogen bonds is observed in protein-DNA complexes. More importantly, more strong hydrogen bonds are observed in the minor grooves of highly specific protein-DNA complexes than multispecific complexes indicating the role of minor groove hydrogen bonds in protein-DNA binding specificity. The knowledge gained from these analyses was applied to develop a novel hydrogen bond energy-based method to assess the similarity between protein-DNA complex models and reference structures, an important step towards computational prediction of complex structures. We show that HBE based method provides more accurate assessment of similarity for models generated by both homology modeling and computational docking methods.

doctoral dissertations

Bioinformatics
Computer science

Ph.D.

Comparison Of Complexes
Computational Models
Hydrogen Bond
Hydrogen Bond Energy
Protein-Dna Complexes
Protein-Ligand

Bioinformatics

Guo, Jun-tao

Weller, Jennifer
Sung, Way
Yan, Shan

Thesis (Ph.D.)--University of North Carolina at Charlotte, 2022.

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Malik_uncc_0694D_13064

http://hdl.handle.net/20.500.13093/etd:2772