ACS Omega· 2026Q1
pdb2reaction : End-to-End Reaction-Path Elucidation from PDB Structures Using Machine-Learning Interatomic Potentials
- 1citations
- Q1SCImago
- 2026year
Short summary
pdb2reaction is an open-source Python toolkit that automates the entire enzymatic reaction mechanism elucidation pipeline directly from PDB structures using a single machine-learning interatomic potential (MLIP) backend, recovering known mechanisms for 19 out of 23 reaction steps in a benchmark.
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Key points
- pdb2reaction automates enzymatic reaction mechanism elucidation from PDB structures using a single MLIP backend.
- It employs a GPU-accelerated fork of pysisyphus for heavy computations and a bond-change-driven recursive path search algorithm.
- The toolkit successfully identified the two-step reaction mechanism of geranyl pyrophosphate C6-methyltransferase BezA, including transition states and intermediates, without prior geometry input.
- On a benchmark of 23 reaction steps across six enzymes, the UMA-m-1.1 backend reproduced literature mechanisms for 19 steps.
AI-generated from the title and abstract; the full text is not read.
Abstract
Abstract Elucidating enzymatic reaction mechanisms requires a sequence of computational tasks comprising active-site extraction, minimum-energy-path search, transition-state (TS) refinement, intrinsic reaction coordinate (IRC) validation, and quasi-rigid-rotor harmonic-oscillator (QRRHO) thermochemistry─stages typically connected by ad hoc scripting and per-system tuning. We present pdb2reaction, an open-source Python command-line toolkit that automates this entire pipeline directly from a user-curated PDB using a single machine-learning interatomic potential (MLIP) backend. A GPU-accelerated pysisyphus fork is bundled to perform the Hessian-based heavy computations─Hessian, IRC, and vibrational analysis─on the same CUDA device as the MLIP for the default backend, minimizing data transfer overhead. This toolkit also implements a bond-change-driven recursive path-search algorithm, which recovered the two-step reaction mechanism of the geranyl pyrophosphate C6-methyltransferase BezA─an SN2-like methyl transfer followed by glutamate-mediated deprotonation via a cationic intermediate─locating both transition states and the intermediate itself without a user-supplied intermediate geometry: from a reactant-state active-site cluster and a minimal scan list, and independently from the reactant and product structures alone. On a benchmark of 23 reaction steps across six enzymes, the broadest-coverage backend, UMA-m-1.1, reproduced the literature mechanism for 19 steps, each with a single imaginary frequency at the transition state. For BezA, all five backends recovered the same two-step pathway and the same rate-limiting step. pdb2reaction enables rapid PDB-to-mechanism elucidation on a single GPU, providing a high-throughput complement to higher-cost DFT-based cluster-model calculations and full enzyme–solvent QM/MM calculations.
The authors' abstract, as published at the source. ACS Omega, 2026 · DOI ↗
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Field: Atomic and Molecular Physics, and Optics
Atomic and Molecular Physics, and OpticsPhysics and Astronomy