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ME models present considerable computational challenges: they are much (&gt;30 times) larger than corresponding metabolic reconstructions (M models), are multiscale, and growth maximization is a nonlinear programming (NLP) problem, mainly due to macromolecule dilution constraints.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Here, we address these computational challenges. We develop a fast and numerically reliable solution method for growth maximization in ME models using a quad-precision NLP solver (Quad MINOS). Our method was up to 45 % faster than binary search for six significant digits in growth rate. We also develop a fast, quad-precision flux variability analysis that is accelerated (up to 60\u00d7 speedup) via solver warm-starts. Finally, we employ the tools developed to investigate growth-coupled succinate overproduction, accounting for proteome constraints.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Just as genome-scale metabolic reconstructions have become an invaluable tool for computational and systems biologists, we anticipate that these fast and numerically reliable ME solution methods will accelerate the wide-spread adoption of ME models for researchers in these fields.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12859-016-1240-1","type":"journal-article","created":{"date-parts":[[2016,9,22]],"date-time":"2016-09-22T12:50:02Z","timestamp":1474548602000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["solveME: fast and reliable solution of nonlinear ME models"],"prefix":"10.1186","volume":"17","author":[{"given":"Laurence","family":"Yang","sequence":"first","affiliation":[]},{"given":"Ding","family":"Ma","sequence":"additional","affiliation":[]},{"given":"Ali","family":"Ebrahim","sequence":"additional","affiliation":[]},{"given":"Colton J.","family":"Lloyd","sequence":"additional","affiliation":[]},{"given":"Michael A.","family":"Saunders","sequence":"additional","affiliation":[]},{"given":"Bernhard O.","family":"Palsson","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2016,9,22]]},"reference":[{"key":"1240_CR1","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/j.cell.2015.05.019","volume":"161","author":"EJ O\u2019Brien","year":"2015","unstructured":"O\u2019Brien EJ, Monk JM, Palsson BO. 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