{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T12:50:22Z","timestamp":1761310222098},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2004,9,7]],"date-time":"2004-09-07T00:00:00Z","timestamp":1094515200000},"content-version":"vor","delay-in-days":3721,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Comput Chem"],"published-print":{"date-parts":[[1994,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Molecular dynamics (MD) simulation and thermodynamic integration (TI) techniques have been used to study the relative free energies of the 8\u2010methyl\u2010N5\u2010deazapterin and 8\u2010methyl\u2010pterin cations (N3 protonated) in aqueous solution. The MD simulations were performed at constant temperature and volume, and the mutations between the cations were carried out by changing the coupling parameter continuously and linearly with the MD simulation time (continuous coupling or slow growth method). The free energy changes have been calculated using both linear and nonlinear couplings of the potential energy functions. Free energy changes have also been computed using the perturbation method for comparison. After separation into electrostatic and van der Waals mutations, most (ca. 80%) of the total free energy change is found to be due to mutation of the electrostatic terms. The free energy change is found to be sensitive to the cutoff radii for interactions between solvent molecules, but rather insensitive to the cutoff radii for interactions between cation and solvent. The free energy changes have also been calculated using various cation and solvent models. Atomic charges for the cations were derived from the molecular electrostatic potential at the semiempirical AM1 and <jats:italic>ab initio<\/jats:italic> self\u2010consistent field (SCF) (3\u201021G, 6\u201031G, 6\u201031G*, 6\u2010311G**) levels using AM1 and 3\u201021G optimized geometries. The TIP3P and SPC models were adopted for the solvent. For the TIP3P solvent model, the order of the free energy change is 6\u201031G &gt; 3\u201021G &gt; 6\u201031G* \u2248 6\u2010311G** &gt; AM1, where the difference between 6\u201031G and AM1 is approximately 1 kcal\/mol. The free energies obtained using 3\u201021G optimized geometries are approximately 0.7 kcal\/mol larger than those obtained using AM1 geometries for the cations. The free energy change computed using the TIP3P\/6\u2010311G* model is 0.3 kcal\/mol larger than that obtained for the SPC\/6\u2010311G* model. \u00a9 1994 by John Wiley &amp; Sons, Inc.<\/jats:p>","DOI":"10.1002\/jcc.540150704","type":"journal-article","created":{"date-parts":[[2005,1,2]],"date-time":"2005-01-02T01:05:38Z","timestamp":1104627938000},"page":"704-718","source":"Crossref","is-referenced-by-count":14,"title":["Thermodynamic integration calculations on the relative free energies of complex ions in aqueous solution: Application to ligands of dihydrofolate reductase"],"prefix":"10.1002","volume":"15","author":[{"given":"Peter L.","family":"Cummins","sequence":"first","affiliation":[]},{"given":"Jill E.","family":"Gready","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2004,9,7]]},"reference":[{"key":"e_1_2_1_2_2","series-title":"Ann. NY Acad. 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