![]() ![]() Peptide and protein datasets used in the study and the precalculated pI for the PDB and some of the most frequently used proteomes are available for large-scale analysis and future development. Moreover, the prediction of pI using the IPC pKa’s leads to fewer outliers, i.e., predictions affected by errors greater than a given threshold. According to the presented benchmarks, the newly developed IPC pKa sets outperform previous algorithms by at least 14.9 % for proteins and 0.9 % for peptides (on average, 22.1 % and 59.6 %, respectively), which corresponds to an average error of the pI estimation equal to 0.87 and 0.25 pH units for proteins and peptides, respectively. Here, I present the Isoelectric Point Calculator (IPC), a web service and a standalone program for the accurate estimation of protein and peptide pI using different sets of dissociation constant (pKa) values, including two new computationally optimized pKa sets. Additionally, pI estimation can be helpful during protein crystallization trials. Combining this ansatz with another previously reported by our group to estimate pKa values we are able to reproduce the isoelectric points of 13 amino acids with no titrable side chains with MAE = 0.4636 pI units.read more read lessĪbstract: Accurate estimation of the isoelectric point (pI) based on the amino acid sequence is useful for many analytical biochemistry and proteomics techniques such as 2-D polyacrylamide gel electrophoresis, or capillary isoelectric focusing used in combination with high-throughput mass spectrometry. These models were validated with tests sets (N = 5) with mean absolute error (MAE) values of 0.1213 (primary), 0.4407 (secondary), and 0.3057 (tertiary). By correlating the minimum surface electrostatic potential (VS,min) on the nitrogen atom of several aliphatic amino groups-calculated at the density functional theory (DFT) ωB97X-D/cc-pVDZ level of theory-we obtained regression models for each kind of substitution pattern from which we interpolate their corresponding pKb values with remarkable accuracy: primary R2 = 0.9519 secondary R2 = 0.9112 and tertiary R2 = 0.8172 (N = 20 for each family). Abstract: Theoretical calculation of equilibrium dissociation constants is a very computationally demanding and time-consuming process since it requires an extremely accurate computation of the solvation free energy changes for each of the species involved. ![]()
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