Proteins ionizable groups

The stoichiometry of complexation for the other proteins was also investigated according to the same analytical procedures [1, 2, 5]. There was good agreement between the number of protein ionizable groups estimated from the Mg values and those from the known amino acid sequence (see Table 18.2), except in the case of the Hb/KPVS complex. The Hb/KPVS complex was investigated in order to further determine the properties of the ternary KPVS/Hb/PDDA... 

Use of the finite-difference PB (FDPB) method to calculate the self- and interaction-energies of the ionizable groups in the protein and solvent. 

In molecular mechanics and molecular dynamics studies of proteins, assig-ment of standard, non-dynamical ionization states of protein titratable groups is a common practice. This assumption seems to be well justified because proton exchange times between protein and solution usually far exceed the time range of the MD simulations. We investigated to what extent the assumed protonation state of a protein influences its molecular dynamics trajectory, and how often our titration algorithm predicted ionization states identical to those imposed on the groups, when applied to a set of structures derived from a molecular dynamics trajectory [34]. As a model we took the bovine... 

Gilson, M. K. Multiple-site titration and molecular modeling Two rapid methods for computing energies and forces for ionizable groups in proteins. Proteins Struct. Punct. Genet. 15 (1993) 266-282. 

Despite the intrinsically nonspecific nature of ion-exchange and reversed-phase/hydrophobic interactions, it is often found that chromatographic techniques based on these interactions can exhibit remarkable resolution this is attributed to the dynamics of multisite interactions being different for proteins having differing surface distributions of hydrophobic and/or ionizable groups. 

ST Russell, A Warshel. Calculations of electrostatic energies m proteins The energetics of ionized groups m bovine pancreatic trypsin inhibitor. J Mol Biol 185 389-404, 1985. 

Table 3-2. Typical range of pK values for ionizable groups in proteins.

One way in which to probe the structural surroundings of a protein is to monitor the pH behavior of specific carbon sites of the C probes. pH-titration studies, of given resonances, had previously been used for probing of the protein structure, because they are known to provide information concerning electrostatic (salt-bridging) interactions in the protein, neighboring group-ionizations, and local environments. ... 

Since electrostatic effects dominate the thermodynamic cycle as shown in Figure 10-2, major development efforts have focused on the calculation of electrostatic energy for transferring the neutral and charged forms of the ionizable group from water with dielectric constant of about 80 to the protein with a low dielectric constant (see later discussions). This led to the development of continuum based models, where water and protein are described as uniform dielectric media, and enter into the linearized Poisson-Boltzmann (PB) electrostatic equation,... 

Bashford D, Karplus M (1990) pKa s of ionizable groups in proteins Atomic detail from a continuum electrostatic model. Biochemistry 29 10219-10225. 

Each type of ionizable group in proteins will have a unique pKa based upon the theoretical value for the amino acid and modulated from that value by its own surrounding microenvironment. Minute environmental changes will cause amine containing residues at different structural locations to have different ionization potentials, even if the groups are otherwise chemically identical. 

With multiple ionizable groups, such as in amino acids and proteins, each group titrates separately according to its pKa. The titration curves shown in Fig. 23-5 are for the amino acids glycine, histidine, and glutamate. 

At ordinary pressure all the ionizable groups have their specific pK values and are present in ionized states according to these values. When pressure increases, we can expect all pK values to change, whereby the overall ionized state of the protein is changed. The whole hydration sheet may also be changed around the protein and conformational rearrangements may occur. This fact indicates that the volume of a protein may be very pressure-dependent. 

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