Biology subjects

Temple, B.

Publications and source records attributed to Temple, B..

3 recordsLinked to original sources

bioRxiv2026

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

Hydrogen-deuterium exchange mass spectrometry (HDX-MS) provides powerful insight into protein structure and dynamics, but interpretation of protection patterns at atomic resolution often requires complementary computational modeling. We present PHENOMS, an open-source Python package that integrates molecular dynamics trajectories with HDX-MS data to analyze backbone hydrogen-bond networks by tracking how individual hydrogen bonds and residue-residue contacts form, break, and reorganize throughout the simulations. This residue-level analysis can reveal local structural changes that may be missed by conventional global trajectory metrics. PHENOMS employs a multithreaded, Rust-accelerated computational engine that achieved an average 16-fold speedup (up to 100-fold) over widely used Python-based MD analysis packages in our benchmarks, while retaining individual hydrogen-bond resolution in every trajectory frame. We demonstrate PHENOMS through multiple retrospective case studies using published and in-house datasets, showing that it can recapitulate HDX-MS protection patterns, identify key residues that drive coordinated structural changes, and benchmark the computational efficiency of the approach. With automated quality-control workflows, PHENOMS provides a framework for integrating hydrogen-bond analysis with HDX-MS data or serves as a standalone, high-throughput tool for analyzing MD trajectories for broader applications in protein engineering, drug discovery, and structural biology.

biophysics↗

bioRxiv2025

Coro1A and TRIM67 collaborate in netrin-dependent neuronal morphogenesis

Neuronal morphogenesis depends on extracellular guidance cues accurately instructing intracellular cytoskeletal remodeling. Here, we describe a novel role for the actin binding protein Coronin 1A (Coro1A) in neuronal morphogenesis, where it mediates responses to the axon guidance cue netrin-1. We found that Coro1A localizes to growth cones and filopodial structures and is required for netrindependent axon turning, branching, and corpus callosum development. We previously discovered that Coro1A interacts with TRIM67, a brain enriched E3 ubiquitin ligase that interacts with a netrin receptor and is also required for netrin-mediated neuronal morphogenesis. Loss of Coro1A and loss of TRIM67 shared similar phenotypes, suggesting that they may function together in the same netrin pathway. A Coro1A mutant deficient in binding TRIM67 was not able to rescue loss of Coro1A phenotypes, indicating that the interaction between Coro1A and TRIM67 is required for netrin responses. Together, our findings reveal that Coro1A is required for proper neuronal morphogenesis, where it collaborates with TRIM67 downstream of netrin.

cell biology↗

bioRxiv2018

Cdt1 variants reveal unanticipated aspects of interactions with Cyclin/CDK and MCM important for normal genome replication.

The earliest step in DNA replication is origin licensing which is the DNA loading of MCM helicase complexes. The Cdt1 protein is essential for MCM loading during G1 phase of the cell cycle, yet the mechanism of Cdt1 function is still incompletely understood. We examined a collection of rare Cdt1 variants that cause a form of primordial dwarfism (Meier-Gorlin syndrome) plus one hypomorphic Drosophila allele to shed light on Cdt1 function. Three hypomorphic variants load MCM less efficiently than WT Cdt1, and their lower activity correlates with impaired MCM binding. A structural homology model of the human Cdt1-MCM complex position the altered Cdt1 residues at two distinct interfaces rather than the previously described single MCM interaction domain. Surprisingly, one dwarfism allele (Cdt1-A66T) is more active than WT Cdt1. This hypermorphic variant binds both Cyclin A and SCFSkp2 poorly relative to WT Cdt1. Detailed quantitative live cell imaging analysis demonstrated no change in stability of this variant however. Instead, we propose that Cyclin A/CDK inhibits Cdt1 licensing function independently of the creation of the SCFSkp2 phosphodegron. Together, these findings identify key Cdt1 interactions required for both efficient origin licensing and tight Cdt1 regulation to ensure normal cell proliferation and genome stability.

molecular biology↗