PubMed Health⌕ Search

Biomedical subjects

B H Honig

Publications and source records attributed to B H Honig.

6 recordsLinked to original sources
PubMed1988

Energetics of charge-charge interactions in proteins.

Electrostatic interactions between pairs of atoms in proteins are calculated with a model based on the linearized Poisson-Boltzmann equation. The equation is solved accurately by a method that takes into account the detailed shape of the protein. This paper presents applications to several systems. Experimental data for the interaction of ionized residues with an active site histidine in subtilisin BPN' allow the model to be tested, using various assumptions for the electrical properties of the protein and solvent. The electrostatic stabilization of the active site thiolate of rhodanese is analyzed, with attention to the influence of alpha-helices. Finally, relationships between electrostatic potential and charge-charge distance are reported for large and small globular proteins. The above results are compared with those of simpler electrostatic models, including Coulomb's law with both a distance-dependent dielectric constant (epsilon = R) and a fixed dielectric constant (epsilon = 2), and Tanford-Kirkwood theory. The primary conclusions are as follows: 1) The Poisson-Boltzmann model agrees with the subtilisin data over a range of ionic strengths; 2) two alpha-helices generate a large potential in the active site of rhodanese; 3) epsilon = R overestimates weak electrostatic interactions but yields relatively good results for strong ones; 4) Tanford-Kirkwood theory is a useful approximation to detailed solutions of the linearized Poisson-Boltzmann equation in globular proteins; and 5) the modified Tanford-Kirkwood theory over-screens the measured electrostatic interactions in subtilisin.

Binding Sites↗
PubMed1988

Analysis of the factors that influence the C=N stretching frequency of polyene Schiff bases. Implications for bacteriorhodopsin and rhodopsin.

In this study quantum mechanical calculations of force constants and normal mode analysis are used to elucidate the factors that influence the C=C and C=N stretching frequencies in polyenes and in protonated Schiff bases. The C=N stretching frequency is found to depend on both the C=N stretching force constant and the C=N-H bending force constant. Due to the contributions of these two modes, the C=N stretching frequency is particularly sensitive to the magnitude of the Schiff base counterion interactions and to the hydrogen bonding environment of the Schiff base nitrogen. Models for chromophore-protein interactions in the retinal binding site and for the photochemical transformations of bacteriorhodopsin and rhodopsin are evaluated in light of these results.

Bacteriorhodopsins↗
PubMed1984

Stability of "salt bridges" in membrane proteins.

We estimate the free energies of transfer of ionized amino acid side chains in water to both their ion-paired and neutral hydrogen-bonded states in low-dielectric media. The difference between the two free energies corresponds to the proton transfer free energy in a "salt bridge" formed between acidic and basic groups (i.e., lysine and glutamic acid residues). Our approach is to use gas phase proton transfer data, pK values, and experimentally determined solvation energies to estimate the standard state free energy changes involved in transferring amino acid side chains, in both ionized and neutral form, from water (dielectric constant epsilon = 80) to vacuum (epsilon = 1). The familiar expressions for the charging energy of a sphere and dipole are used to interpolate between epsilon = 1 and epsilon = 80. Our results suggest that it costs approximately 10-16 kcal/mol to transfer a salt bridge from water to a medium of epsilon = 2-4, in ionized or neutral form within the resolution of our estimates. The proton transfer energy is thus approximately 0. The tendency of salt bridges to form additional hydrogen bonds in real proteins suggests that the ion pair will be present in most biological systems.

Calorimetry↗
PubMedDate not supplied

Calculation of electrostatic potentials in an enzyme active site.

To be able to calculate the contributions of individual amino acids to the electrostatic field of a protein would be of considerable value in designing proteins of enhanced or altered function and stability. Recent studies on the serine protease subtilisin provide direct measurements of the electrostatic potential in the active site of the enzyme produced by two charged amino acids. We have used these results to test a recently developed method for the calculation of electrostatic interactions between two specific sites on a protein. The extent of agreement between the theoretical and experimental results suggests that the continuum solvent model used in the calculations reproduces the essential features of the interaction.

Binding Sites↗