Explanation of the Biochemical Compound Declarative Database

Overview

Klotho takes a high-level description of a compound's stereochemical configuration and uses a graph grammar to generate a number of alternative representations (B. Dunford-Shore and T. Kazic, in preparation). Those internal to Klotho are informationally equivalent to the high-level description, while those external to Klotho (isomeric SMILES string and PDB file) necessarily lose significant information. However, the isomeric SMILES string is a common format, and has the virtue of being the input to CONCORD (TM) , which generates a pseudo energy-minimized structure. The resulting PDB files are then passed to RasMol , and a single image is captured as a gif file. A Fischer-type projection is generated from one of Klotho's internal representations by some additional code we have developed.

Our aim in Klotho was to develop a stereochemically correct representation for compound structures which would permit us to describe the chemical and enzymatic mechanisms of biochemical reactions the way biochemists do . Since functional descriptions necessarily entail structures, we began with those. We gradually developed a procedure for checking the grammar by encoding molecules, computing the Fischer and PDB files, and examining the high-level description and the resulting compounds. Since we use an isomeric SMILES string as input for generating the PDB file, we implicitly check the accuracy of the former as well. As we accumulate compounds we have been placing their extensional representations on the Web.

Assumptions Underlying the Representation

The compounds are represented in a consistent manner, under the following assumptions.

• All structures are drawn at pH 7.0. In each case, we intend to represent the predominant ionized form for each substituent group at that pH. In some cases we have made educated guesses, so if you think you know better please let us know.

• All structures are represented in the standard projections used in biochemistry. We have added slightly to the Fischer convention by bolding bonds emanating from chiral centers, and have included the common device of showing hemiacetal rings by a long looping bond. Of course compounds with aromatic substituents are not displayed in this projection.

• Bonds with a solid line and a dashed line are resonant among the identical groups. For example, at this pH carboxyls and phosphoryls will include resonant oxygens.

• Each compound is numbered and named as biochemists do, and as specifically as possible. We have included synonyms which are equally specific, either by name or by custom, but do not consider more general terms synonyms (for example, ``glucose'' is not synonymous with ``beta-D-glucopyranose'').

• Many substituent groups can be displayed as well; their names are based on the original compound, with the position of the "missing" groups numbered and signalled by the term "yl" in the name.

Checking and Viewing the Compounds

Each compound has been checked by several different people at different times. We occasionally find errors in structural diagrams; we try to resolve these by examining crystal structures, finding more authoritative diagrams, and considering the biochemistry of reactions which synthesize or degrade the compound. We will not post dubious compounds, but occasionally find we have erred after posting.

You may be surprised by the three dimensional views: because the carbon backbone zigzags in and out of the plane, spatial presentations will not be identical to the Fischer projections in the plane. We have found model-building helpful in learning how to zigzag in our heads. The substituents of a carbon below a plane running through the mean of the carbon positions will be flipped left-right relative to the Fischer projection, while substituents of carbons above will look like the Fischer projection. For open chain carbohydrates, the first chiral carbon from the top should be out of the plane (and therefore equivalent to Fischer). For the cyclic sugars, the ring oxygen is in the back. If you haven't implemented the Chemical MIME type , you can download the PDB file and view it in your favorite viewer , and rotate the structures to your heart's content. If you still believe there is an error, please don't hesitate to contact us .

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