Biomedical subjects

A W Edith Chan

Publications and source records attributed to A W Edith Chan.

3 recordsLinked to original sources

PubMed2004

PDBLIG: classification of small molecular protein binding in the Protein Data Bank.

It is known that proteins can adopt different folds while sharing similar features for recognition of similar substrates or ligands, for example, in the binding sites of enzyme cofactors such as ATP. On the other hand, proteins that have highly flexible binding sites or belong to large and diverse protein families can bind structurally dissimilar ligands, as, for example, in the case of the matrix metalloprotease family. We have developed a database, PDBLIG, that classifies protein domains and ligands. The information stored includes each protein's function, domain class(es), which ligand(s) it binds, and so on. The database can provide valuable knowledge for drug discovery, supporting the answering of questions such as whether the same drug molecule can bind different target protein families and whether these families are related functionally or structurally, which ligand classes (such as metabolites or organic molecules) bind to a particular protein family and whether the ligands are druglike, and which target families bind a wide variety of ligands and whether different ligands are associated with different subfamilies.

Binding Sites↗

PubMed2002

Bioinformatics and protein design.

Traditionally, the development of drugs has focused on small molecule therapeutics. However, with recent advances in recombinant protein technology the potential of proteins as therapeutics is starting to be realized. Already there are protein drugs on the market, including naturally occurring proteins, engineered proteins and proteins introduced into the patient by way of gene therapy. The next generation of such drugs are likely to be designed molecules; proteins devised from scratch and specifically tailored to have a required 3-dimensional structure and biochemical function. The key to such de novo design is the extensive bioinformatics knowledge that has been obtained from experimentally determined protein structures during the past 40-50 years. The knowledge is far from complete; for example, the protein folding problem has not yet been completely solved. Despite this, bioinformatics plays a crucial role in protein design, as is outlined in this review, and a number of de novo protein structures have been successfully designed in recent years. Some examples of these successes, which are available in the Protein Data Bank, are presented. They suggest that carefully designed protein therapeutics are a genuine prospect for the future.

Animals↗

PubMed1999

Efficient discovery of inhibitory ligands for diverse targets from a small combinatorial chemical library of chimeric molecules.

Living systems are mainly composed and regulated by compounds in four biochemical classes and their polymers-nucleotides, carbohydrates, lipids, and amino acids. Early combinatorial chemistry libraries consisted of peptides. The present report describes the general bioactivity and biophysical properties of a combinatorial chemical library that used glyco, nucleotidyl, and lipid building blocks. The resulting chimeric combinatorial library of 361 compounds had a confirmed cumulative hit rate of 0.16%, which is 8-fold higher than a commonly claimed industrial benchmark of 0. 02%. It produced 7 structurally confirmed hits for a third of 12 proprietary drug discovery projects, and these comprised a variety of molecular targets. Diversity analyses demonstrated that despite the small number of compounds, a wider range of diversity space was covered by this library of biochemical chimeras than by a branched tripeptide library of the same size and similar generic formula.

Binding Sites↗