αCharges

AlphaCharges (αCharges) is a web application for the calculation of partial atomic charges on protein structures predicted by the AlphaFold2 algorithm and deposited in the AlphaFoldDB database. The charges are computed by the SQE+qp empirical method, which quality is comparable to quantum mechanical charge calculation approaches (specifically, it is parameterized using B3LYP/6-31G*/NPA quantum mechanical charges). Before computation of the charges, αCharges protonates the input protein structures by PROPKA3. The details about the methodology and usage are described in the manual. This website is free and open to all users and there is no login requirement. Source codes are freely available at GitHub.

Examples

P-glycoprotein
P-glycoprotein
P-glycoprotein is part of the ABC transporter proteins that decrease drug accumulation in cancer cells (Leslie2005). It is a 170-kDa protein which consists of a nucleotide-binding domain and a transmembrane domain (Ward2013). Partial atomic charges calculated by αCharges demonstrate the differences in charge distribution between transmembrane parts and the extracellular/intracellular one.
Pepsin
Pepsin is the enzyme that is majorly involved in protein digestion in the stomach. It is secreted as a zymogen and activated by the acidic pH created by the stomach parietal cells. Pepsin is the most effective at a pH of approximately 1.5 to 2, and it becomes inactive when the pH rises above 6 (Heda2022). Pepsin remains structurally stable until at least a pH of 8. Differences in a charge distribution between its active form (pH 2) and inactive form (pH 8) can be seen in this use case. The alkaline environment causes an increase in negative charges, which contributes to the structural instability of the pepsin, causing the shift to an inactive form of the protein (Tanaka2001, Grahame2021).
PIN proteins
pin
The PIN family proteins control plant growth by regulating auxin export from the cytosol to the extracellular space. Eight types of PIN proteins are known (PIN1-PIN8), and last year, structures of three of them were discovered and published in Nature (i.e., articles about PIN1, PIN3, PIN8). Partial atomic charges play an important role in PINs functionality. The PIN protein part inside the cytosol (containing the cytosolic loop) is charged more than the part outside the cytosol. Questionable is the charge distribution of PIN5, which structure differs from other PINs (Ung2022) and was not experimentally determined yet. In the use case, you can compare the charge distribution of AlphaFold2 predicted PINs from A. thaliana.
If you found αCharges helpful, please cite: Schindler, O., Berka, K., Cantara, A., Křenek, A., Tichý, D., Raček, T., & Svobodová, R. (2023). αCharges: Partial atomic charges for AlphaFold structures in high quality. Nucleic Acids Research. Are you interested in a research collaboration? Feel free to contact us.
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αCharges tool is a part of services provided by ELIXIR – European research infrastructure for biological information.
For other services provided by ELIXIR's Czech Republic Node visit www.elixir-czech.cz/services.
Licence conditions in accordance with § 11 of Act No. 130/2002 Coll. The owner of the software is Masaryk University, a public university, ID: 00216224. Masaryk University allows other companies and individuals to use this software free of charge and without territorial restrictions in usual way, that does not depreciate its value. This permission is granted for the duration of property rights. This software is not subject to special information treatment according to Act No. 412/2005 Coll., as amended. In case that a person who will use the software under this licence offer violates the licence terms, the permission to use the software terminates.