Absolute and Relative Binding Free Energy Calculations of Nucleotides to Multiple Protein Classes.

ABSTRACT: Polyphosphate nucleotides, such as ATP, ADP, GTP, and GDP, play a crucial role in modulating protein functions through binding and/or catalytically activating proteins (enzymes). However, accurately calculating the binding free energies for these charged and flexible ligands poses challenges due to slow conformational relaxation and the limitations of force fields. In this study, we examine the accuracy and reliability of alchemical free energy simulations with fixed-charge force fields for the binding of four nucleotides to nine proteins of various classes, including kinases, ATPases, and GTPases. Our results indicate that the alchemical simulations effectively reproduce experimental binding free energies for all proteins that do not undergo significant conformational changes between thei

SUBMITTER: Purohit A 

PROVIDER: S-EPMC11859759 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature