Stephen H. Bryant (bryant@ncbi.nlm.nih.gov)
National Center for Biotechnology Information (NCBI),
National Library of Medicine, National Institutes of
Health,
Bethesda, MD 20894, USA.
NCBI maintains a database combining biological sequences and
associated Medline citations. This information may be accessed
over the Internet via an easy-to-use browser, Entrez. With Entrez
one may rapidly discover what is known about a biological
molecule, exploring "links" between sequences and citations, the
homologous "neighbors" of a sequence, and "neighbor" citations,
which discuss the structure and function of related molecules. A
recent addition to Entrez is information describing 3-dimensional
structure, allowing one to examine directly the structure of a
biological molecule or its homologs.
The 3-dimensional structure database used by Entrez is called
MMDB, for Molecular Modeling Data Base. It consists of messages in
the ASN.1 language, which are translated automatically to in-
memory data structures using C routines available in the NCBI
toolkit. The MMDB data specification gives a complete description
of the chemical structure of a macromolecular assembly, with
unambiguous linkage to atomic coordinates. This data organization
is intended to facilitate the computations required for homology
modeling, which is based on alignment of the residue sequence, or,
more generally, on comparison of the chemical graphs of different
molecules, including their non-polymer components.
NCBI supports an active research program in comparative molecular
analysis techniques which make use of 3-dimensional structure
information. Computational methods for sequence-structure
"threading" provide a means to generate model structures for
proteins which are very distantly related to a protein of known
structure. Methods for rapid structure-structure comparison
provide a means to detect architectural similarities and/or
distant evolutionary relationships among proteins of known
structure. These methods currently make use of the NCBI "PKB"
research database. In the near future, however, they will operate
as client software accessing MMDB, and in this way provide
examples of how applications developed elsewhere may make use of
this resource.