PHENOMS: Open-Source Software for Rust-Accelerated Hydrogen-Bond Analysis in Molecular Dynamics Simulations

Hydrogen-deuterium exchange mass spectrometry (HDX-MS) offers valuable insights into protein structure and dynamics, but deciphering protection patterns at the atomic level typically necessitates supplementary computational modeling. The authors introduce PHENOMS, an open-source Python package designed to merge molecular dynamics trajectories with HDX-MS data, facilitating the examination of backbone hydrogen-bond networks by monitoring the formation, dissolution, and reorganization of individual hydrogen bonds and residue-residue contacts throughout simulations.

This residue-level analysis can unveil subtle local structural alterations that might be overlooked by traditional global trajectory metrics.

To enhance computational efficiency, PHENOMS leverages a multithreaded, Rust-accelerated computational engine. Benchmarking against other widely-used Python-based MD analysis packages revealed that PHENOMS achieved an average 16-fold speedup (potentially reaching 100-fold), all while preserving individual hydrogen-bond resolution in every trajectory frame.

The authors validated PHENOMS through several retrospective case studies utilizing both published and in-house datasets. Their findings demonstrated that PHENOMS could accurately replicate HDX-MS protection patterns, pinpoint critical residues driving coordinated structural changes, and evaluate the computational efficiency of the approach.

With integrated quality-control workflows, PHENOMS offers a comprehensive framework for combining hydrogen-bond analysis with HDX-MS data or serves as a standalone, high-throughput tool for scrutinizing MD trajectories, finding utility in various domains such as protein engineering, drug discovery, and structural biology.