Parametrized Models of Aqueous Free Energies of Solvation Based on Pairwise Descreening of Solute Atomic Charges from a Dielectric Medium

Hawkins, Gregory D.; Cramer, Christopher J.; Truhlar, Donald G.

doi:10.1021/jp961710n

Cited by 850 publications

(976 citation statements)

References 44 publications

Supporting

Mentioning

959

Contrasting

Unclassified

Order By: Relevance

“…10,13,24,26,27 However, its performance on larger molecules has generally not been as good, with the trend being more pronounced for molecules having large interior regions. 24,26 Since the GB model shares the same underlying physical approximation-continuum electrostatics-with the PB approach, it is natural, in optimizing the GB performance, to use the PB model as a reference.…”

Section: Improving the Generalized Born Approximationmentioning

confidence: 99%

“…Second, approximations are introduced for the integration of this energy density over the molecular region, typically in order to obtain an expression involving only a sum over atom pairs. 27,28 The result is summarized as…”

Section: A New Model For Effective Born Radiimentioning

confidence: 99%

“…In a popular GB model, 27 which we refer to as GB HCT (Hawkins, Cramer, Truhlar), the three-dimensional (3D) integral in the above equation is performed over the VDW spheres of solute atoms outside of the atom i whose effective radius is being calculated (the step-function ensures that the volume of atom i itself is excluded from the integration). This implies a definition of the solute volume in terms of a set of spheres, rather than the complex molecular surface 29 commonly used in the PB calculations.…”

Section: A New Model For Effective Born Radiimentioning

confidence: 99%

“…This allows one to obtain a relatively simple analytical form for R i . A closed-form analytical expression for two overlapping spheres, from which I can be derived in the pairwise approximation, is given in Hawkins et al 27 and Schaefer and Froemmel. 28 It was also shown 10 that using slightly reduced values of ˜i ϭ i Ϫ 0.09 Å instead of i in Eqs.…”

Section: A New Model For Effective Born Radiimentioning

confidence: 99%

“…25 This error is expected to be greatest for deeply buried atoms characterized by large effective radii, while for the surface atoms, it is largely canceled by the opposing error arising from the Coulomb approximation, which tends 11,15,28 to overestimate R i . Since the GB HCT model was parameterized and shown 13,27 to perform very well on small molecules with few buried atoms (small effective radii), we focus on improving the procedure to calculate the effective radii for buried atoms in larger compounds, while preserving the good performance of GB HCT for small R i 's. In particular, we retain the use of ˜i ϭ i Ϫ 0.09 Å instead of i .…”

Section: A New Model For Effective Born Radiimentioning

confidence: 99%

See 4 more Smart Citations

Exploring protein native states and large‐scale conformational changes with a modified generalized born model

2004

View full text Add to dashboard Cite

Implicit solvation models provide, for many applications, a reasonably accurate and computationally effective way to describe the electrostatics of aqueous solvation. Here, a popular analytical Generalized Born (GB) solvation model is modified to improve its accuracy in calculating the solvent polarization part of free energy changes in large-scale conformational transitions, such as protein folding. In contrast to an earlier GB model (implemented in the AMBER-6 program), the improved version does not overstabilize the native structures relative to the finite-difference PoissonBoltzmann continuum treatment. In addition to improving the energy balance between folded and unfolded conformers, the algorithm (available in the AMBER-7 and NAB molecular modeling packages) is shown to perform well in more than 50 ns of native-state molecular dynamics (MD) simulations of thioredoxin, protein-A, and ubiquitin, as well as in a simulation of Barnase/Barstar complex formation. For thioredoxin, various combinations of input parameters have been explored, such as the underlying gas-phase force fields and the atomic radii. The best performance is achieved with a previously proposed modification to the torsional potential in the Amber ff99 force field, which yields stable native trajectories for all of the tested proteins, with backbone root-mean-square deviations from the native structures being ϳ1.5 Å after 6 ns of simulation time. The structure of Barnase/Barstar complex is regenerated, starting from an unbound state, to within 1.9 Å relative to the crystal structure of the complex.

show abstract

Section: Improving the Generalized Born Approximationmentioning

confidence: 99%

Section: A New Model For Effective Born Radiimentioning

confidence: 99%

Section: A New Model For Effective Born Radiimentioning

confidence: 99%

Section: A New Model For Effective Born Radiimentioning

confidence: 99%

Section: A New Model For Effective Born Radiimentioning

confidence: 99%

See 3 more Smart Citations

Exploring protein native states and large‐scale conformational changes with a modified generalized born model

2004

View full text Add to dashboard Cite

show abstract

Implicit solvent models: Combining an analytical formulation of continuum electrostatics with simple models of the hydrophobic effect

Wagner

Simonson

1999

J. Comput. Chem.

View full text Add to dashboard Cite

The recent development of approximate analytical formulations of continuum electrostatics opens the possibility of efficient and accurate implicit solvent models for biomolecular simulations. One such formulation (ACE, Schaefer & Karplus, J. Phys. Chem., 1996, 100:1578) is used to compute the electrostatic contribution to solvation and conformational free energies of a set of small solutes and three proteins. Results are compared to finite‐difference solutions of the Poisson equation (FDPB) and explicit solvent simulations and experimental data where available. Small molecule solvation free energies agree with FDPB within 1–1.5 kcal/mol, which is comparable to differences in FDPB due to different surface treatments or different force field parameterizations. Side chain conformation free energies of aspartate and asparagine are in qualitative agreement with explicit solvent simulations, while 74 conformations of a surface loop in the protein Ras are accurately ranked compared to FDPB. Preliminary results for solvation free energies of small alkane and polar solutes suggest that a recent Gaussian model could be used in combination with analytical continuum electrostatics to treat nonpolar interactions. ©1999 John Wiley & Sons, Inc. J Comput Chem 20: 322–335, 1999

show abstract

Universal solvation model based on conductor-like screening model

et al. 2000

Self Cite

View full text Add to dashboard Cite

Atomic surface tensions are parameterized for use with solvation models in which the electrostatic part of the calculation is based on the conductor‐like screening model (COSMO) and the semiempirical molecular orbital methods AM1, PM3, and MNDO/d. The convergence of the calculated polarization free energies with respect to the numerical parameters of the electrostatic calculations is first examined. The accuracy and precision of the calculated values are improved significantly by adjusting two parameters that control the segmentation of the solvent‐accessible surface that is used for the calculations. The accuracy of COSMO calculations is further improved by adopting an optimized set of empirical electrostatic atomic radii. Finally, the electrostatic calculation is combined with SM5‐type atomic surface tension functionals that are used to compute the nonelectrostatic portions of the solvation free energy. All parameterizations are carried out using rigid (R) gas‐phase geometries; this combination (SM5‐type surface tensions, COSMO electrostatics, and rigid geometries) is called SM5CR. Six air–water and 76 water–solvent partition coefficients are added to the training set of air–solvent data points previously used to parameterize the SM5 suite of solvation models, thereby bringing the total number of data points in the training set to 2266. The model yields free energies of solvation and transfer with mean unsigned errors of 0.63, 0.59, and 0.61 kcal/mol for AM1, PM3, and MNDO/d, respectively, over all 2217 data points for neutral solutes in the training set and mean unsigned errors of 3.0, 2.7, and 3.1 kcal/mol, respectively, for 49 data points for the ions. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 340–366, 2000

show abstract

Parametrized Models of Aqueous Free Energies of Solvation Based on Pairwise Descreening of Solute Atomic Charges from a Dielectric Medium

Cited by 850 publications

References 44 publications

Exploring protein native states and large‐scale conformational changes with a modified generalized born model

Exploring protein native states and large‐scale conformational changes with a modified generalized born model

Implicit solvent models: Combining an analytical formulation of continuum electrostatics with simple models of the hydrophobic effect

Universal solvation model based on conductor-like screening model

Contact Info

Product

Resources

About