On the calculation of pK_as in proteins

Abstract

This paper describes a general method to calculate the pKas of ionizable groups in proteins. Electrostatic calculations are carried out using the finite difference Poisson-Boltzmann (FDPB) method. A formal treatment of the calculation of pKas within the framework of the FDPB method is presented. The major change with respect to previous work is the specific incorporation of the complete charge distribution of both the neutral and charged forms of each ionizable group into the formalism. This is extremely important for the treatment of salt bridges. A hybrid statistical mechanical/Tanford-Roxby method, which is found to be significantly faster than previous treatments, is also introduced. This simplifies the problem of summing over the large number of possible ionization states for a complex polyion. Applications to BPTI and serine proteases suggest that the calculations can be quite reliable. However, the necessity of including bound waters in the treatment of the Asp-70... His-31 salt bridge in T4 lysozyme and experience with other proteins suggest that additional factors ultimately need to be considered in a comprehensive treatment of pKas in proteins.

L-2-Hydroxyglutarate production arises from noncanonical enzyme function at acidic pH

“…MCCE2 explores all side chain rotamers. DelPhi 58 was used to solve the Poisson Boltzmann equation to obtain the pairwise interactions between charged and/or polar groups and the solvation energy with an internal dielectric constant of 4.0 and 80 for the solvent, with 0.15 salt concentration. The atomic partial charges and radii for the amino acids were obtained from PARSE 59 , while those of the ligands were generated by QUACPAC (Openeye toolkit 2016-Jun.1).…”

Electrostatic properties of cowpea chlorotic mottle virus and cucumber mosaic virus capsids

“…For the boundary conditions the focusing method was applied. 29,42 Considering the extremely large size of the system, the calculations were performed on the Blue Horizon and Data Star supercomputers using 1000 processors for each run. The dimensions of the CCMV capsid are 271 × 271 × 271 Å 3 and 319 × 319 × 319 Å 3 for the native and swollen forms (Cα model), respectively.…”

Calculation of the isoelectric point of tryptic peptides in the pH 3.5–4.5 range based on adjacent amino acid effects

“…The basic question to be answered is how does the polypeptide environment shift amino acid pK values compared to that of the individual amino acid in an aqueous solution [25]. For example, the equilibrium condition for a charged amino acid between the ionized and neutral states in an aqueous environment is greatly affected by the energy of solvation of the individual species.…”

“…For example, the equilibrium condition for a charged amino acid between the ionized and neutral states in an aqueous environment is greatly affected by the energy of solvation of the individual species. However, in the polypeptide environment interactions with permanent dipoles, electrons, and other charged/ titratable amino acids also must be considered to accurately determine pK values [25][26][27]. In addition, in a hydrophobic environment the pK values of acid groups increase and those of basic groups decrease resulting from the fact that the undissociated form is the favored state [1].…”