{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T13:03:44Z","timestamp":1761743024946},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"21","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Recent advances in cell-free protein expression systems allow specific labeling of proteins with amino acids containing stable isotopes (15N, 13 C and 2H), an important feature for protein structure determination by nuclear magnetic resonance (NMR) spectroscopy. Given this labeling ability, we present a mathematical optimization framework for designing a set of protein isotopomers, or labeling schedules, to reduce the congestion in the NMR spectra. The labeling schedules, which are derived by the optimization of a cost function, are tailored to a specific protein and NMR experiment.<\/jats:p><jats:p>Results: For 2D 15N-1H HSQC experiments, we can produce an exact solution using a dynamic programming algorithm in under 2 h on a standard desktop machine. Applying the method to a standard benchmark protein, calmodulin, we are able to reduce the number of overlaps in the 500 MHz HSQC spectrum from 10 to 1 using four samples with a true cost function, and 10 to 4 if the cost function is derived from statistical estimates. On a set of 448 curated proteins from the BMRB database, we are able to reduce the relative percent congestion by 84.9% in their HSQC spectra using only four samples. Our method can be applied in a high-throughput manner on a proteomic scale using the server we developed. On a 100-node cluster, optimal schedules can be computed for every protein coded for in the human genome in less than a month.<\/jats:p><jats:p>Availability: A server for creating labeling schedules for 15N-1H HSQC experiments as well as results for each of the individual 448 proteins used in the test set is available at http:\/\/nmr.proteomics.ics.uci.edu.<\/jats:p><jats:p>Contact: \u00a0pfbaldi@ics.uci.edu<\/jats:p><jats:p>Supplementary information: Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btm406","type":"journal-article","created":{"date-parts":[[2007,9,26]],"date-time":"2007-09-26T02:14:39Z","timestamp":1190772879000},"page":"2829-2835","source":"Crossref","is-referenced-by-count":6,"title":["Minimizing the overlap problem in protein NMR: a computational framework for precision amino acid labeling"],"prefix":"10.1093","volume":"23","author":[{"given":"Michael J.","family":"Sweredoski","sequence":"first","affiliation":[{"name":"1 Department of Computer Science, 2Department of Chemistry and 3Institute for Genomics and Bioinformatics, University of California, Irvine, USA"},{"name":"1 Department of Computer Science, 2Department of Chemistry and 3Institute for Genomics and Bioinformatics, University of California, Irvine, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin J.","family":"Donovan","sequence":"additional","affiliation":[{"name":"1 Department of Computer Science, 2Department of Chemistry and 3Institute for Genomics and Bioinformatics, University of California, Irvine, USA"},{"name":"1 Department of Computer Science, 2Department of Chemistry and 3Institute for Genomics and Bioinformatics, University of California, Irvine, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bao D.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"1 Department of Computer Science, 2Department of Chemistry and 3Institute for Genomics and Bioinformatics, University of California, Irvine, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.J.","family":"Shaka","sequence":"additional","affiliation":[{"name":"1 Department of Computer Science, 2Department of Chemistry and 3Institute for Genomics and Bioinformatics, University of California, Irvine, USA"},{"name":"1 Department of Computer Science, 2Department of Chemistry and 3Institute for Genomics and Bioinformatics, University of California, Irvine, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Baldi","sequence":"additional","affiliation":[{"name":"1 Department of Computer Science, 2Department of Chemistry and 3Institute for Genomics and Bioinformatics, University of California, Irvine, USA"},{"name":"1 Department of Computer Science, 2Department of Chemistry and 3Institute for Genomics and Bioinformatics, University of California, Irvine, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2007,9,25]]},"reference":[{"key":"2023041107265472100_","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0009-2614(80)80041-8","article-title":"Natural abundance N-15 NMR by enhanced heteronuclear spectroscopy","volume":"69","author":"Bodenhausen","year":"1980","journal-title":"Chem. 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