#20 · Structural bio & protein design
Fused protein language model embeddings predict enzyme, variant, and kinase properties
The shared thread is moving beyond a single sequence embedding toward multimodal fusion or context-aware representation. AltereGO combines score-level predictions from four protein representations for Gene Ontology molecular function, and KINBERT pairs a protein language model with phospho-PCA pooled screening and Bayesian hierarchical modeling for kinase-substrate interactions. SAEKP fuses enzyme and substrate representations with a site attention module that reweights them to predict kcat, Km, and Ki. MIL-BC instead represents proteins as bags of automatically detected domains for EC number prediction, improving F1 by 0.03-0.17 over a sequence baseline. AdventML and ESMRank are less representation-centric: AdventML predicts optimal temperature from transformer embeddings with resampling for extremes, and ESMRank applies learning-to-rank with overlap-aware rank fusion across about 1100 deep mutational scans. The items do not share a single method; what is new is the emphasis on combining modalities or explicit site and domain structure.
Preprints
PHENOMS: Open-Source Software for Rust-Accelerated Hydrogen-Bond Analysis in Molecular Dynamics Simulations
PHENOMS is an open-source, Rust-accelerated Python package that analyzes backbone hydrogen-bond networks in MD trajectories and integrates them with HDX-MS…
Multi-Ensemble Reweighting Enables Structural Interpretation of Differential HDX-MS
Introduces multi-ensemble maximum-entropy reweighting that handles shared peptide-dependent deuterium loss in differential HDX-MS, validated on LeuT and NCX_Mj…
FoXSight: Facilitating Computational Hit Identification in Crystallographic Fragment Screening Experiments
FoXSight uses Difference-of-Gaussian filtering on multi-reference subtraction maps to detect recurring ligand-bound density in crystallographic fragment…
Facilitating the identification of cryo-EM hit matter in drug discovery with Astex-Faro
Astex-Faro is a statistical framework that flags significant density deviations in cryo-EM maps against a reference ensemble, with a new FSCoh consistency…
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