Published February 21, 2026 | Version v1
Preprint Open

Electrostatic Desynchronization as a Mechanism of Drug Resistance: A Hypothesis Integrating Charge Field Redistribution and Ligand-Receptor Binding Dynamics

Authors/Creators

  • 1. Pesquisa Indepentente

Description

Here, we propose that drug resistance may not only occur through increased metabolism and other pharmacokinetic circumstances. This subject may be far more complex than it appears. Our preprint emphasizes the condition of drug expulsion from the receptor, mainly due to desynchronized electrostatic forces, which prevent the ligand from binding in a manner that is, let's say, properly adjusted to the receptor protein.

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Dates

Available
2026-02-21

References

  • Chau & Dean. Electrostatic complementarity between proteins and ligands. J Comput Aided Mol Des. 1994. DOI:10.1007/BF00123665 — foundational work defining electrostatic complementarity in receptor-ligand binding.
  • Dukhovich & Darkhovskii. Molecular electrostatic potential as a factor of drugreceptor recognition. J Mol Recognit. 2003 — illustrates role of electrostatic compensation in ligand binding
  • Recent work on electrostatic models emphasizes quantitative roles of electrostatics vs shape complementarity in scoring functions.
  • Example of electrostatic change influencing resistance: replacement of D-Ala with DLac in bacterial peptidoglycan introduces repulsive interactions that explain vancomycin resistance biophysically