Unlocking precision in aptamer engineering: a case study of the thrombin binding aptamer illustrates why modification size, quantity, and position matter.

ABSTRACT: The thrombin binding aptamer (TBA) is a prototypical platform used to understand the impact of chemically-modified nucleotides on aptamer stability and target affinity. To provide structural insight into the experimentally-observed effects of modification size, location, and number on aptamer performance, long time-scale molecular dynamics (MD) simulations were performed on multiple binding orientations of TBA-thrombin complexes that contain a large, flexible tryptophan thymine derivative (T-W) or a truncated analogue (T-K). Depending on modification position, T-W alters aptamer-target binding orientations, fine-tunes aptamer-target interactions, strengthens networks of nucleic acid-protein contacts, and/or induces target conformational changes to enhance binding. The proximity and 5'-to-3

SUBMITTER: Murray MT 

PROVIDER: S-EPMC11472061 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature