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bioRxiv · 10.1101/2022.02.02.478804

patcHwork: A user-friendly pH sensitivity analysis web server for protein sequences and structures

Schmitz, M.·Schultze, A.·Vanags, R.·Voigt, K.·Di Ventura, B.·Oeztuerk, M. A.
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Abstract

pH regulates protein function and interactions by altering the charge of individual residues causing the loss or gain of intra-molecular non-covalent bonds, which may additionally lead to structural rearrangements. While tools to analyze residue-specific charge distribution of protein sequences and structures at a given pH exist, currently no tool is available to investigate non-covalent bond changes at two different pH values. In an effort to make protein pH sensitivity analysis more accessible to researchers without computational structural biology background, we developed patcHwork, a web server that combines the identification of amino acids undergoing a charge shift with the determination of affected non-covalent bonds at two user-defined pH values. At the sequence-only level, patcHwork applies the Henderson-Hasselbalch equation to determine pH-sensitive residues. When the 3D protein structure is available, patcHwork can be employed to gain a deeper mechanistic understanding of the effect of pH on a protein of interest. This is achieved using the PDB2PQR and PROPKA tools and non-covalent bond determination algorithms. A user-friendly interface allows visualizing pH-sensitive residues as well as affected salt bridges, hydrogen bonds and aromatic (pi-pi and cation-pi) interactions. Importantly, patcHwork can be used to identify patches, a new concept we propose of pH-sensitive residues in close proximity on the protein structure, which may have a major impact on function. We demonstrate the attractiveness of patcHwork studying experimentally investigated pH-sensitive proteins. (Access:https://patchwork.biologie.uni-freiburg.de/) Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/478804v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@df873eorg.highwire.dtl.DTLVardef@12815a4org.highwire.dtl.DTLVardef@a4d718org.highwire.dtl.DTLVardef@256c10_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Schmitz, M., Schultze, A., Vanags, R., Voigt, K., Di Ventura, B., Oeztuerk, M. A.. 2022-02-04. patcHwork: A user-friendly pH sensitivity analysis web server for protein sequences and structures. https://doi.org/10.1101/2022.02.02.478804

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