Identifying the minimal sets of distance restraints for FRET-assisted protein structural modeling

• Published in: ArXiv.org 2024-08
• Main Authors: Liu, Zhuoyi, Grigas, Alex T, Sumner, Jacob, Knab, Edward, Davis, Caitlin M, O'Hern, Corey S
• Format: Article
• Language: English
• ISSN: 2331-8422; 2331-8422

Proteins naturally occur in crowded cellular environments and interact with other proteins, nucleic acids, and organelles. Since most previous experimental protein structure determination techniques require that proteins occur in idealized, non-physiological environments, the effects of realistic cellular environments on protein structure are largely unexplored. Recently, Förster resonance energy transfer (FRET) has been shown to be an effective experimental method for investigating protein structure . Inter-residue distances measured can be incorporated as restraints in molecular dynamics (MD) simulations to model protein structural dynamics . Since most FRET studies only obtain inter-residue separations for a small number of amino acid pairs, it is important to determine the minimum number of restraints in the MD simulations that are required to achieve a given root-mean-square deviation (RMSD) from the experimental structural ensemble. Further, what is the optimal method for selecting these inter-residue restraints? Here, we implement several methods for selecting the most important FRET pairs and determine the number of pairs that are needed to induce conformational changes in proteins between two experimentally determined structures. We find that enforcing only a small fraction of restraints, , where is the number of amino acids, can induce the conformational changes. These results establish the efficacy of FRET-assisted MD simulations for atomic scale structural modeling of proteins .