Solvation free energies calculated using the GB/SA model: Sensitivity of results on charge sets, protocols, and force fields

✍ Scribed by Reddy, M. Rami; Erion, Mark D.; Agarwal, Atul; Viswanadhan, Vellarkad N.; McDonald, D. Quentin; Still, W. Clark

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 236 KB
• Volume: 19
• Category: Article
• ISSN: 0192-8651
• DOI: 10.1002/(sici)1096-987x(199805)19:7<769::aid-jcc7>3.0.co;2-o

✦ Synopsis

The sensitivity of aqueous solvation free energies SFEs , estimated using the GBrSA continuum solvent model, on charge sets, protocols, and force fields, was studied. Simple energy calculations using the GBrSA solvent model were performed on 11 monofunctional organic compounds. Results indicate that calculated SFEs are strongly dependent on the charge sets. Charges derived from electrostatic potential fitting to high level ab initio wave functions using the CHELPG procedure and ''class IV'' charges from AM1rCM1a or PM3rCM1p calculations yielded better results than the corresponding Mulliken charges. Calculated SFEs were similar to MCrFEP energies obtained in the presence of explicit TIP4P water. Further improvements were obtained by UU UU Ž . using GVBr6-31G and MP2r6-31 q G CHELPG charge sets that included correlation effects. SFEs calculated using charge sets assigned by the OPLSA U Ž U U

force field gave the best results of all standard force fields MM2 , MM3 , U U . MMFF, AMBER , and OPLSA implemented in MacroModel. Comparison of relative and absolute SFEs computed using either the GBrSA continuum model or MCrFEP calculations in the presence of explicit TIP4P water showed that, in general, relative SFEs can be estimated with greater accuracy. A second set of 20 mono-and difunctional molecules was also studied and relative SFEs estimated Ž . using energy minimization and thermodynamic cycle perturbation TCP protocols. SFEs calculated from TCP calculations using the GBrSA model were Ž sensitive to bond lengths of dummy bonds i.e., bonds involving dummy . atoms . In such cases, keeping the bond lengths of dummy bonds close to the