Molecular Docking Emerges as a Central Tool in PET Probe Development

Molecular docking, a computational technique that predicts how ligands bind to their biological targets, has become an indispensable auxiliary tool in the development of positron emission tomography (PET) probes, according to a review published in EJNMMI Radiopharmacy and Chemistry. PET is an advanced imaging modality that enables visualization of molecular and cellular processes, and PET probes are its critical core component. The review, published as an open access article on 31 August 2026, surveys the current status of molecular docking across the entire PET probe development pipeline and outlines its future prospects.

The authors begin by introducing the fundamental principles of molecular docking, covering its core algorithms, scoring functions, and the software packages commonly used in practice. Driven by breakthroughs in structural biology and computational technology, the technique has evolved from a niche method into a routine component of modern radiotracer design, the review states.

A substantial portion of the review examines how docking supports lead compound discovery through virtual screening, in which large compound libraries are computationally evaluated for their ability to bind a chosen biological target. It also describes rational structural optimization along three complementary dimensions: reinforcing favorable interactions between the ligand and its target, eliminating unfavorable factors that may impair binding or probe performance, and the rational design of radiolabeling sites. Beyond these design-stage applications, the authors note the widespread use of retrospective analysis of binding modes, in which docking is applied after the fact to interpret how existing probes interact with their targets.

The review further addresses the systematic computational evaluation of existing probes, with a particular focus on tau-targeted tracers used in PET imaging. In this area, molecular docking has been used to compare binding sites, subtype selectivity, and off-target mechanisms across multiple probes and distinct tau fibril isoforms. Such analyses allow researchers to rationalize differences in how related tracers behave against the same protein target family.

In its conclusions, the review characterizes molecular docking as a comprehensive tool for PET probe development while acknowledging an important limitation: current applications remain predominantly retrospective rather than prospective. Nevertheless, the authors argue that with continuous breakthroughs and deep integration of technologies such as high-precision structure prediction and GPU-accelerated ultra-large-scale screening, molecular docking is poised to become a key enabler for the rational development of PET probes.

Subject of Research: The applications and future prospects of molecular docking in PET probe development

Article Title: Current status and prospects of molecular docking in PET probe development

Article References: Chen, Y., Jin, C., Hong, L., Fang, Z., Zhang, H., Chen, Y., Chen, L., Wang, J., Zhong, Y., Tian, M., & Zhang, H. (2026). Current status and prospects of molecular docking in PET probe development. EJNMMI Radiopharmacy and Chemistry. https://doi.org/10.1186/s41181-026-00492-6

Image Credits: AI Generated

DOI: 10.1186/s41181-026-00492-6

Keywords: molecular docking, PET probes, positron emission tomography, virtual screening, tau tracers, radiolabeling, scoring functions, structural biology, computational chemistry, radiopharmacy, Current, status