Unleashing Molecular Insights with Combined Constant pH Molecular Dynamics and Free Energy Calculations

Constant pH molecular dynamics (CPHMD) and free energy calculations are useful for
studying biological systems in solution. Integrating these two methods makes it
possible to investigate complex pH-dependent phenomena and obtain insights into
their underlying thermodynamics and kinetics. Furthermore, recent advances in
computational power and methodology have enabled the application of this combined
approach to increasingly larger and more complex systems, providing valuable
information for drug discovery, enzyme engineering, and biophysical research. In this
study, we showed how the combination of CpHMD and ABF modified the binding
profiles of the R5Pi protein, an essential protein of the pentose pathway of
Trypanosoma cruzi, according to the protonation state of the receptor.