Bidstrup Foundation Undergraduate Fellowship for Kacey Clark | About | Beckstein Lab

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Bidstrup Foundation Undergraduate Fellowship for Kacey Clark

Bidstrup Foundation Undergraduate Fellowship for Kacey Clark

Physics freshwoman undergraduate student Kacey Clark was selected as a Bidstrup Undergraduate Fellow for the 2016-2017 academic year. The Bidstrup Fellowship is awarded by Barrett, The Honors College at Arizona State University where Kacey is a student.

Kacey has already been working in the Beckstein Lab for the last year, starting with an involvement in the BioXFEL Villages outreach program Experiencing Molecules when she was still a high school student.

Project: Data Mining the Protein Data Bank for Ion-Protein Interactions

Proteins fulfill vital functions in living cells as enzymes, as molecular machines, or with structural roles. About 40% of all proteins require metal ions to function1 and an unknown number rely on interactions with inorganic anions2. In order to develop an understanding of the mechanistic role of such ion-protein interactions, we first need to quantify the ion binding geometry. The Protein Data Bank (PDB) contains over 120,000 experimental structure of proteins, many of them containing ions. The goal of this project is to develop a computational pipeline to search the whole Protein Data Bank and characterize the binding geometries of cations and anions. Because every year almost 10,000 new structures are added, the development of a website that automatically reruns this analysis with every weekly update of the PDB and updates results in real time would serve to continually increase the accuracy of the analysis.

Specific Aims

  1. Compute coordination statistics for metal cations (e.g. sodium, potassium, lithium, and thallium).
  2. Compute coordination statistics for anions (e.g. chloride, fluoride, carboxylate, sulfate).
  3. Make results available as a web page; make code available under an open source license.
  4. Automate computations so that the web site is updated automatically after each update of the PDB.
  5. Write and submit a research paper.


Ion binding can be characterized by the type of atoms in close contact and their distances from the ion. Metal ions are cations (positively charged ions) and tend to interact with negatively charged or negatively polarized atoms, particularly oxygen3. Inorganic anions (negatively charged ions) are coordinated by positively polarized atoms such as nitrogen and hydrogen atoms attached to oxygen (O-H) or nitrogen atoms (N-H)2. An important quantitative measure of the ion-neighboring atom coordination geometries are distance distributions of the neighboring atoms relative to the ion, also known as radial distribution functions (RDFs) in solution4. From an RDF, the number of closest neighbors, the “first solvation shell”, and closest distances can be computed. Second solvation shells can also be discerned. RDFs also directly enable quantitative comparison of the coordination of ions in proteins to the coordination in bulk water.

Preliminary Work

Functions to query the PDB, download all structures with metal cations (Na+, K+, Li+, Tl+), and to calculate RDFs of oxygen atoms around these ions were implemented in the Python programming language and developed as open source PDB_Ion_Survey code (released under the GNU General Public License, v3). Qualitatively, oxygen atoms form distinct first and second coordination shells around Na+ and K+, similar to the coordination of ions in water (as seen in simulations).

Proposed Work

Based on the preliminary work, (1) the precise location and size of coordination shells must be determined by collecting data from all all ion-bound structures in the PDB. (2) Interactions between anions and proteins, about which little is known, should be investigated. The dependence of the cation and anion coordination data on a number of factors such as structure resolution, protein function, ion location relative to active sites, the presence of water, and the function of the ion (ligand, inhibitor, etc.) will be assessed. (3) Results will be made available as a web page and (4) continuously updated by automatically running the analysis whenever the PDB is updated. (5) This project should result in the submission of a research paper.


  1. a C. Andreini, I. Bertini, G. Cavallaro, G. L. Holliday, and J. M. Thornton. Metal ions in biological catalysis: from enzyme databases to general principles. J Biol Inorg Chem, 13(8):1205–18, 2008. doi: 10.1007/s00775-008-0404-5.
  2. a b O. Carugo. Buried chloride stereochemistry in the protein data bank. BMC Struct Biol, 14:19, 2014. doi: 10.1186/s12900-014-0019-8.
  3. a Y. Lu, N. Yeung, N. Sieracki, and N. M. Marshall. Design of functional metalloproteins. Nature, 460(7257): 855–862, 08 2009. doi: 10.1038/nature08304.
  4. a S. Varma and S. B. Rempe. Coordination numbers of alkali metal ions in aqueous solutions. Biophys Chem, 124(3):192–199, 2006. doi: 10.1016/j.bpc.2006.07.002.

Discuss: “Bidstrup Foundation Undergraduate Fellowship for Kacey Clark”

September 09, 2016 at 10:41 am #

Congratulations Kacey! I look forward to working with you on your project.

Well done!


Posted by  Oliver Beckstein

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