Steve Bryant, Ph.D.
NCBI Structure Group
Building 38A, Room 5S504
8600 Rockville Pike
Bethesda, MD 20894
Dr. Bryant's research focuses on design of web-based scientific resources in three areas: structural bioinformatics, protein classification, and chemical biology. His role is as project director, which entails leading and managing professional staff and mentoring trainees in algorithm development research related to improving these resources.
This ongoing project aims to integrate macromolecular three-dimensional structure information into NCBI's molecular information resources. This effort assists molecular-biologist users by providing straightforward access to information on biochemical function and mechanism of action as provided by structure determination. The resource also assists structural biologists by providing tools for detailed comparative analysis of related protein structures. This project in part underpins the Conserved Domain Database, CDD, as its Cn3D molecular graphics tool and structure-neighbor alignments are used extensively in that project. Chemical structures of ligands as extracted from macromolecular structures are also treated as a data source for PubChem.
The Conserved Domain Database (CDD), is NCBI's protein family classification resource. The protein domain-annotation "bubbles" shown with protein BLAST searches and the domain features listed in "GenPept" sequence displays, for example, are derived from CDD. The "bubble" displays alone are currently viewed roughly 55,000 times per day by roughly 30,000 users. Another indication of usage is that 9 papers about CDD, written by my colleagues and I between 2002 and 2011, have been cited over 3,000 times. Continuing effort by my colleagues and I has been required to improve the performance of software tools for phylogenetic classification and to apply these methods systematically to annotate thousands of functionally distinct protein domain families.
PubChem's overall goal is to provide an open repository for information related to the biological activities of small molecules and web-accessible tools for search and analysis enabling scientific discovery. PubChem is presented via NCBI's "Entrez" biomedical search engine. Users may easily search PubChem's chemical structure database for compounds of interest by chemical name, for example, and link to any associated bioactivity results in PubChem's Bioassay database. While Entrez's indices and cross-links are a powerful tool for finding records of interest, additional tools summarize bioactivity results over multiple tests and multiple compounds. Entrez easily lists bioassays in which a set of compounds shows activity, for example, and a user may then "drill down" to PubChem's "Bioactivity Summary" to rank bioassays by the number of actives. Or the user may drill down further to PubChem's "Structure-Activity Analysis" tool to cluster compounds by structural similarity and bioassays by activity-profile similarity. Drilling further, a detailed and searchable "Bioassay Results" data table is available. For Web and programmatic access, tools to mine the bioactivity test results within Entrez Bioassay records are critical.
Shoemaker BA, Zhang D, Thangudu RR, Tyagi M, Fong JH, Marchler-Bauer A, Bryant SH, Madej T, Panchenko AR. Inferred Biomolecular Interaction Server--a web server to analyze and predict protein interacting partners and binding sites. Nucleic Acids Res. 2010;38(Database issue):D518-24.
Thangudu RR, Tyagi M, Shoemaker BA, Bryant SH, Panchenko AR, Madej T. Knowledge-based annotation of small molecule binding sites in proteins. BMC Bioinformatics. 2010;11:365.
Marchler-Bauer A, Lu S, Anderson JB, Chitsaz F, Derbyshire MK, DeWeese-Scott C, Fong JH, Geer LY, Geer RC, Gonzales NR, Gwadz M, Hurwitz DI, Jackson JD, Ke Z, Lanczycki CJ, Lu F, Marchler GH, Mullokandov M, Omelchenko MV, Robertson CL, Song JS, Thanki N, Yamashita RA, Zhang D, Zhang N, Zheng C, Bryant SH. CDD: a Conserved Domain Database for the functional annotation of proteins. Nucleic Acids Res. 2011;39(Database issue):D225-9.
Bolton EE, Chen J, Kim S, Han L, He S, Shi W, Simonyan V, Sun Y, Thiessen PA, Wang J, Yu B, Zhang J, Bryant SH. PubChem3D: a new resource for scientists. J Cheminform. 2011;3(1):32.
Li Q, Cheng T, Wang Y, Bryant SH. PubChem as a public resource for drug discovery. Drug Discov Today. 2010;15(23-24):1052-7.