ISSN:
0192-8651
Keywords:
Computational Chemistry and Molecular Modeling
;
Biochemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
,
Computer Science
Notes:
Molecular dynamics (MD) simulation and thermodynamic integration (TI) techniques have been used to study the relative free energies of the 8-methyl-N5-deazapterin and 8-methyl-pterin 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 ab initio self-consistent field (SCF) (3-21G, 6-31G, 6-31G*, 6-311G**) levels using AM1 and 3-21G 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 6-31G 〉 3-21G 〉 6-31G* ≈ 6-311G** 〉 AM1, where the difference between 6-31G and AM1 is approximately 1 kcal/mol. The free energies obtained using 3-21G 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/6-311G* model is 0.3 kcal/mol larger than that obtained for the SPC/6-311G* model. © 1994 by John Wiley & Sons, Inc.
Additional Material:
6 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jcc.540150704
