Strong and weak hydrogen bonds in drug-DNA complexes: A statistical analysis |
| |
Authors: | Sunil K Panigrahi Gautam R Desiraju |
| |
Institution: | (1) School of Chemistry, University of Hyderabad, Hyderabad, 500 046, India |
| |
Abstract: | A statistical analysis of strong and weak hydrogen bonds in the minor groove of DNA was carried out for a set of 70 drug-DNA
complexes. The terms ‘strong’ and ‘weak’ pertain to the inherent strengths and weakness of the donor and acceptor fragments
rather than to any energy considerations. The dataset was extracted from the protein data bank (PDB). The analysis was performed
with an in-house software, hydrogen bond analysis tool (HBAT). In addition to strong hydrogen bonds such as O—H⋯O and N—H⋯O,
the ubiquitous presence of weak hydrogen bonds such as C—H⋯O is implicated in molecular recognition. On an average, there
are 1.4 weak hydrogen bonds for every strong hydrogen bond. For both categories of interaction, the N(3) of purine and the
O(2) of pyrimidine are favoured acceptors. Donor multifurcation is common with the donors generally present in the drug molecules,
and shared by hydrogen bond acceptors in the minor groove. Bifurcation and trifurcation are most commonly observed. The metrics
for strong hydrogen bonds are consistent with established trends. The geometries are variable for weak hydrogen bonds. A database
of recognition geometries for 26 literature amidinium-based inhibitors of Human African Trypanosomes (HAT) was generated with
a docking study using seven inhibitors which occur in published crystal structures included in the list of 70 complexes mentioned
above, and 19 inhibitors for which the drug-DNA complex crystal structures are unknown. The virtual geometries so generated
correlate well with published activities for these 26 inhibitors, justifying our assumption that strong and weak hydrogen
bonds are optimized in the active site. |
| |
Keywords: | Docking drug-DNA complexes Human African Trypanosome hydrogen bond Protein Data Bank |
本文献已被 PubMed SpringerLink 等数据库收录! |
|