Elucidating the Conformational Dependence of Calculated pK_a Values

Abstract

The variability within calculated protein residue pKa values calculated using Poisson-Boltzmann continuum theory with respect to small conformational fluctuations is investigated. As a general rule, sites buried in the protein core have the largest pKa fluctuations but the least amount of conformational variability; conversely, sites on the protein surface generally have large conformational fluctuations but very small pKa fluctuations. These results occur because of the heterogeneous or uniform nature of the electrostatic microenvironments at the protein core or surface, respectively. Atypical surface sites with large pKa fluctuations occur at the interfaces between significant anionic and cationic potentials.

Unraveling HIV protease flaps dynamics by Constant pH Molecular Dynamics simulations

“…The residues pk a is structure-dependent, since the proton lability is influenced by the micro-environment to which the amino acid is subjected. Therefore, it is likely that as the structure changes as a function of the pH, the pk a also changes, suffering an indirect effect of the changes in pH (Livesay et al, 2006 andDi Russo et al, 2012).…”

Effect of methylation on the side-chain pKavalue of arginine

“…A study in 2007 attempted to determine p K a of lysine and arginine on apo‐calmodulin using NMR titrations; they reported only slight chemical shift perturbations for arginine at pH 12.5, indicating that the p K a has not yet been reached . In addition, several groups have recently published simulated or predicted arginine or guanidine variants p K a values with mixed results ranging from 12.5 to 16.1 . Recently, the p K a of free arginine using potentiometry and arginine using 1 H, 13 C, and 15 N NMR titrations was published at ≥13.8 .…”

“…34 In addition, several groups have recently published simulated or predicted arginine or guanidine variants pK a values with mixed results ranging from 12.5 to 16.1. [42][43][44][45][46] Recently, the pK a of free arginine using potentiometry and arginine using 1 H, 13 C, and 15 N NMR titrations was published at 13.8. 24 Although this value is somewhat lower than the one reported here, it was stated that the reported value of 13.8 could be an underestimation.…”

How accurate and statistically robust are catalytic site predictions based on closeness centrality?

“…Solvent accessibility is calculated using DSSP [42], which is an extremely fast approach. DSSP calculated solvent accessibilities range between 0 to >250 Å 2 .…”