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

Abstract

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

Simple models for nonpolar solvation: Parameterization and testing

“…The three nonpolar terms are used along with GB, either individually or in various combinations. Thus, one model is the GBSA model we have applied extensively to protein design; another model combines GB and LK (GBLK model), as proposed earlier . Two other models combine GB with the explicit dispersion term and either a SA or an LK term (GBDISA, GBDILK models).…”

Metal‐Catalyzed Derivatization of Cα‐Tetrasubstituted Amino Acids and Their Use in the Synthesis of Cyclic Peptides

“…For charges highly exposed to solvent or deeply buried inside a solute, the GB screening function is expected to be reasonably accurate. For example, good agreement with FDPB calculations, MD with explicit solvent, and experimental data are obtained for the solvation of small organic molecules 30, 34–36, 38–41. However, for moderately buried charges, the physics of the GB models may depart from the full dielectric continuum model.…”

“…Therefore, careful parameterization and testing are needed to determine the usefulness of GB for large biomolecules. Current GB variants have given good results for solvation and conformational free energies of polypeptides,42 nucleic acids,43 and, to a lesser extent, proteins 35, 37, 40, 41, 44, 45. Recently, GB was used for the first time in molecular dynamics simulations of DNA and RNA46, 47 and of three proteins 29, 41, 48.…”

A physically meaningful method for the comparison of potential energy functions

“…Among the most common such measures, one may find the root mean square deviation (RMSD) [1,6,13,14,16], the mean error of the energies (ER) [1,7,10], the standard deviation of the error (SDER) [7], the mean of the absolute error (AER) [11], all of which have units of energy, and the Pearson's correlation coefficient r [2, 4, 6, 7, 10, 15, 19], which does not have units. Finally, in [16], a root mean square of the difference in the relative energies (REL) (see Eq.…”

“…Others tackle the problem of designing new algorithms to perform this calculation looking for the improvement of the relation between accuracy and numerical complexity [8][9][10][11][12][13][14][15][16][17][18][19].…”