S4: HDDB2, a macromolecular structure database

HDDB2, a macromolecular structure database prototype for the annotation of macromolecular structures from QM calculations, neutron scattering and X-ray crystallography studies at sub-atomic resolution
Raul Cachau, Frederick National Laboratory for Cancer Research, Leidos Biomed, USA

Raul E. Cachau


Frederick National Laboratory for Cancer Research,
Leidos Biomed, USA


Biomacromolecules (Proteins, DNA, RNA) are frequently described as aggregates of repeats as its polymeric structure suggests. The chemical interpretation of biomacromolecules structure indicates a great variability in its properties suggesting an alternative description of the macromolecule as collections of unique microenvironments instead.

This can be seen in the large deviations of pKa values observed for titratable groups present in different protein environments, or the unique properties exhibit by aminoacid side chains in reaction centers. Recent advances in neutron scattering, ultra-high (sub-atomic) resolution crystallography and the development of refined computational tools allows the exploration of biomolecular microenvironments at an ever increasing level of detail.

There is, however, a gap in our growing understanding of biomacromolecular structure and our ability to store and retrieve this information in a meaningful way. A recent effort at collecting and cataloging this information has resulted in the experimental HHDB2 database, based on early efforts to catalog neutron scattering data (HHDB, http://hhdb01.tokai-sc.jaea.go.jp/HHDB/) including extensions to accommodate the information obtained from QM calculations.

Based on the results catalogued on this database and our own analysis of ultra-high resolution structures we have begun the characterization of microenvironments showing the largest deviations from average geometries and occupations in crystal structures. Of particular interest has been the observation of an increasing number of pyramidalized nitrogens in peptide bonds, revealing the presence of H-bond acceptor nitrogens in the backbone. Other interesting results include the direct observation of carbons with labile hydrogens.

The methods employed to characterize these motifs and the impact of them in our understanding of protein function will be reviewed in this presentation.