Linking Sequence and Structure
with Function

California Institute for Quantitative Biosciences (QB3)
University of California San Francisco
1700 4th Street, 5th Floor
San Francisco, CA 94158
USA


daniel goes hereDaniel E. Almonacid, Ph.D.
Postdoctoral Scholar

Research Summary

My main scientific curiosity lies in the structure-function relationship in proteins. I am deeply interested on how the amino acid residues that compose proteins are capable of modulating their catalytic and binding affinities, and on how the events of gene duplication, sequence divergence and gene combination have generated the hundreds of different catalytic and binding affinities expressed by enzymes in living organisms. I am currently working on the use of sequence similarity networks as an alternative to phylogenetic trees for the analysis of evolutionary relatedness in large sets of sequences. I am also working on the classification of enzyme functions based on ligand and reaction similarities, as opposed to the more common sequence/structure similarity.

 

Education and Work Experience

Dec '07 - Present Postdoctoral Scholar in Biopharmaceutical Sciences
Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, USA
Postdoctoral work under the supervision of Prof. Patricia Babbitt, looking at using enzymes as a model to develop new classification schemes for proteins based on quantitative measures of reaction and ligand similarities [7,8]. We will use the resulting classification schemes to inform approaches for functional annotation of sequences and structures of unknown activity and to help find existing templates for engineering enzymes with novel activities.

 

Oct '04 - Nov '07 PhD Chemistry
Unilever Centre for Molecular Science Informatics, and St. John's College, University of Cambridge, UK
Thesis title: The Chemistry and Evolution of Protein Catalysis.
Research, supervised by Dr John Mitchell, focused on understanding the repertoire of enzyme catalysis and the function of catalytic amino acid residues [6]. The work helped producing the MACiE database [1,2,9], an electronic database of enzyme reaction mechanisms, helped the development of novel algorithms to measure enzyme similarity [5], and quantified the effects of conservation of binding and chemistry in divergent evolution.

 

Mar '99 - Sep '04 BSc Biochemistry First-Class degree
Department of Biochemistry and Molecular Biology, and Department of Physical Chemistry, Universidad de Concepción, Chile
Thesis title: Intra-Phycocyanin and Inter-Phycocyanin Preferential Light Transfer Pathways in Phycobilisomes.
Research, supervised by Dr Marta Bunster and Dr Adelio Matamala, focused on the elucidation of the structure-function relationship in the light-harvesting protein Phycocyanin from different species using semi-empirical calculations and protein-protein docking [3,4].

 

Other Science-Related Activities

 

Publications

[9] MACiE: exploring the diversity of biochemical reactions.
Gemma L. Holliday, Claudia Andreini, Julia D. Fischer, Syed Asad Rahman, Daniel E. Almonacid, Sophie T. Williams and William R. Pearson. Nucleic Acids Research 40: D783-D789 (2012)

[8] Toward mechanistic classification of enzyme functions.
Daniel E. Almonacid and Patricia C. Babbitt. Current Opinion in Chemical Biology 15: 435-442 (2011)

[7] Quantitative comparison of catalytic mechanisms and overall reactions in convergently evolved enzymes: implications for classification of enzyme function.
Daniel E. Almonacid, Emmanuel R. Yera, John B. O. Mitchell and Patricia C. Babbitt. PLoS Computational Biology 6: e1000700 (2010)

[6] The Chemistry of Protein Catalysis.
Gemma L. Holliday, Daniel E. Almonacid, John B. O. Mitchell and Janet M. Thornton. Journal of Molecular Biology 372: 1261-1277 (2007)

[5] Using reaction mechanism to measure enzyme similarity.
Noel M. O'Boyle, Gemma L. Holliday, Daniel E. Almonacid and John B. O. Mitchell. Journal of Molecular Biology 368: 1484-1499 (2007)

[4] A Semiempirical Approach to the Intra-Phycocyanin and Inter-Phycocyanin Fluorescence Resonance Energy-Transfer Pathways in Phycobilisomes.
Adelio R. Matamala, Daniel E. Almonacid, Maximiliano F. Figueroa, José Martínez-Oyanedel and Marta C. Bunster. Journal of Computational Chemistry, 28: 1200-1207 (2007)

[3] The structure at 2 A resolution of Phycocyanin from Gracilaria chilensis and the energy transfer network in a PC-PC complex.
Carlos Contreras-Martel, Adelio Matamala, Carola Bruna, German Poo-Caamaño, Daniel Almonacid, Maximiliano Figueroa, José Martínez-Oyanedel and Marta Bunster. Biophysical Chemistry 125: 388-396 (2007)

[2] MACiE (Mechanism, Annotation and Classification in Enzymes): novel tools for searching catalytic mechanisms
Gemma L. Holliday, Daniel E. Almonacid, Gail J. Bartlett, Noel M. O'Boyle, James W. Torrance, Peter Murray-Rust, John B. O. Mitchell and Janet M. Thornton. Nucleic Acids Research 35: D515-D520 (2007)

[1] MACiE: a database of enzyme reaction mechanisms
Gemma L. Holliday, Gail J. Bartlett, Daniel E. Almonacid, Noel M. O'Boyle, Peter Murray-Rust, Janet M. Thornton and John B.O. Mitchell. Bioinformatics 21: 4315-4316 (2005)

 

More Information

You can find more information about my scientific work in my profile at BiomedExperts, and in my curriculum vitae.




Valid XHTML 1.0 Transitional