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

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

CV, updated August 2012

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 have worked on the development of similarity metrics to compare chemical reactions, and have used those algorithms, as well as molecular simlarity algorithms, to compare the function of enzymes. More recently, I have been using sequence similarity networks for the analysis of evolutionary relatedness in large sets of sequences, especially in the isoprenoid synthase superfamily of enzymes.

Keywords / Areas of Interst

enzymes, catalytic residues, reaction similarity, mechanism similarity, sequence similarity, networks, enzyme superfamilies, convergently evolved enzymes, isoprenoid synthases, function annotation, target selection, metabolic reconstruction, binding specificity, catalytic specificity, biological and chemical databases, sequence alignment, phycobilisomes, phycocyanin, fluorescence resonance energy transfer, Gracilaria chilensis, Fremyella diplosiphon, computational biology, cheminformatics, bioinformatics, computational chemistry, scientific networking, diasporas, brain circulation, entrepreneurship

Education and Research Experience

Dec '07 - Present Postdoctoral Scholar in Bioengineering
Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, USA
Supervised by Prof. Patricia Babbitt, I develop and use quantitative metrics of reaction and substrate similarity to compare enzymes from both mechanistically diverse superfamilies and convergently evolved groups [7,8]. Our aim is to create new classifications for enzyme functions based on these quantitative measures [8]. For the past two years I have been part of the Enzyme Function Initiative (EFI), a multidisciplinary collaboration aiming at developing a large-scale sequence/structure-based strategy for assigning the in vitro functions and in vivo contexts of unknown enzymes, involving more than 80 researchers from 14 academic groups across the USA. Here, I use the quantitative metrics described above, in conjunction with sequence similarity networks, to define structure-function relationships to inform function annotation of sequences and structures recently discovered in genome and metagenome projects, and to select the most informative targets for structure and function determination. Recently, we have also been using metrics of reaction and substrate similarities to identify putative metabolic pathways from metabolomics data. Additionally, my work in the EFI has involved extensive examination of the isoprenoid synthase superfamily of enzymes.


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



(Visit he following link to view my public profile at Google Scholar)

[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)
joint first authors

[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

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