PKAD-2: New Entries and Expansion of Functionalities of the Database of Experimentally Measured pKa’s of Proteins

Abstract

Almost all biological reactions are pH-dependent and understanding the origin of pH dependence requires knowledge of the pKa’s of ionizable groups. Here, we report a new edition of PKAD, the PKAD-2, which is a database of experimentally measured pKa’s of proteins, both wild-type and mutant proteins. The new addition includes 117 wild-type and 54 mutant pKa values, resulting in total 1742 experimentally measured pKa’s. The new edition of PKAD-2 includes eight new wild-type and 12 new mutant proteins, resulting in total of 220 proteins. This new edition incorporates a visual 3D image of the highlighted residue of interest within the corresponding protein or protein complex. Hydrogen bonds (HB) were identified, counted and implemented as a search feature. Other new search features include the number of neighboring [Formula: see text][Formula: see text]Å from the heaviest atom of the side chain of a given amino acid. Here, we present PKAD-2 with the intention to continuously incorporate novel features and current data with the goal to be used as a benchmark for computational methods.

Accurate Protein pKa Prediction with Physical Organic Chemistry Guided 3D Protein Representation

“…The 3D structures of all proteins were sourced from the Protein Data Bank (PDB). − To take account of the surrounding environment of protein, small molecules, including water molecules inherent in the protein structures, were retained, and metal centers were also preserved for P-SPOC representation. To enhance the model’s validation, we also incorporated the recently published PKAD-2 database, which offers an updated compilation of protein p K a values, into our subsequent analysis. Further details on data selection and preprocessing are available in the Supporting Information.…”

Progress in protein p<i>K</i>_a prediction

“…2021年12月, 本课题组提出了 国际上首个基于机器学习的蛋白质 预测模型 DeepKa, 证明了引入人工智能方法解决蛋白质 预测问题的可行性 [25] . 本课题组对现有的 数据库PKAD [100]…”

DeepKa Web Server: High-Throughput Protein pKa Prediction

“…However, protein p K a measurements are often time-consuming and expensive. According to PKAD-2, a protein p K a database released recently, only 1742 experimentally measured p K a ’s in 220 proteins are available . Over the past two decades, many computational methods have been developed to complement such characterization by experiment .…”

“…According to PKAD-2, a protein pK a database released recently, only 1742 experimentally measured pK a 's in 220 proteins are available. 8 Over the past two decades, many computational methods have been developed to complement such characterization by experiment. 9 Among these in silico methods, constant pH molecular dynamics (CpHMD) schemes give the most accurate predictions of protein pK a 's.…”