An Integrative Framework for Mapping Orientational Landscapes of Peripheral Membrane Proteins by Paramagnetic NMR and Atomistic Simulation.

ABSTRACT: The functions of peripheral membrane proteins (PMPs) can be critically influenced by their orientations on membrane surfaces, which are inherently dynamic and challenging to characterize with precision. Molecular dynamics (MD) simulations, while powerful, face limitations in force field accuracy and sampling, particularly for systems involving intricate protein-lipid interactions. Here, we employ artifact-free membrane paramagnetic relaxation enhancement (mPRE) data as a quantitative benchmark to evaluate and refine MD simulations of KRas4B, a classical PMP, bound to anionic bilayers. Discrepancies between state-of-the-art simulations and experimental data are quantified and attributed to both inadequate sampling and force field inaccuracies. By fine-tuning the electrostatic interactions b

SUBMITTER: Liu D 

PROVIDER: S-EPMC12188388 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature