Related Experiment Video
Updated: Jun 8, 2026

Determination of the Gas-phase Acidities of Oligopeptides
Published on: June 24, 2013
Electrostatic solvation free energy of amino acid side chain analogs: implications for the validity of electrostatic
Bin Lin1, B Montgomery Pettitt
1Structural and Computational Biology and Molecular Biophysics Program, Baylor College of Medicine, Houston, Texas 77030, USA.
Abstract:
Electrostatic free energies of solvation for 15 neutral amino acid side chain analogs are computed. We compare three methods of varying computational complexity and accuracy for three force fields: free energy simulations, Poisson-Boltzmann (PB), and linear response approximation (LRA) using AMBER, CHARMM, and OPLS-AA force fields. We find that deviations from simulation start at low charges for solutes. The approximate PB and LRA produce an overestimation of electrostatic solvation free energies for most of molecules studied here. These deviations are remarkably systematic. The variations among force fields are almost as large as the variations found among methods. Our study confirms that success of the approximate methods for electrostatic solvation free energies comes from their ability to evaluate free energy differences accurately.
Related Concept Videos
Amino acids
Theory of Strong Electrolytes
The Debye–Hückel Theory of Electrolyte Solutions
Basicity of Aliphatic Amines
To measure the basicity of amines, two conventions are generally used. The first defines Kb as the basicity constant for the deprotonation reaction of water by the amine, as presented in Figure 1. Conventionally, lower Kb indicates higher...
Solvating Effects
Ligand Binding Sites
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
