Multi-scale structural similarity embedding search across entire proteomes

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 6, 2025

Abstract The rapid expansion of three-dimensional (3D) biomolecular structure information, driven by breakthroughs in artificial intelligence/deep learning (AI/DL)-based predictions, has created an urgent need for scalable and efficient similarity search methods. Traditional alignment-based approaches, such as structural superposition tools, are computationally expensive challenging to scale with the vast number available macromolecular structures. Herein, we present a strategy designed navigate extensive repositories experimentally determined structures computed models predicted using AI/DL Our approach leverages protein language deep neural network architecture transform 3D into fixed-length vectors, enabling large-scale comparisons. Although trained predict TM-scores between single-domain structures, our model generalizes beyond domain level, accurately identifying full-length polypeptide chains multimeric assemblies. By integrating vector databases, method facilitates retrieval, addressing growing challenges posed expanding volume biostructure information.

Язык: Английский

Discovery, design, and engineering of enzymes based on molecular retrobiosynthesis

mLife, Год журнала: 2025, Номер unknown

Опубликована: Март 28, 2025

Abstract Biosynthesis—a process utilizing biological systems to synthesize chemical compounds—has emerged as a revolutionary solution 21st‐century challenges due its environmental sustainability, scalability, and high stereoselectivity regioselectivity. Recent advancements in artificial intelligence (AI) are accelerating biosynthesis by enabling intelligent design, construction, optimization of enzymatic reactions systems. We first introduce the molecular retrosynthesis route planning biochemical pathway including single‐step algorithms AI‐based design tools. highlight advantages large language models addressing sparsity data. Furthermore, we review enzyme discovery methods based on sequence structure alignment techniques. Breakthroughs structural prediction expected significantly improve accuracy discovery. also summarize for de novo generation nonnatural or orphan reactions, focusing functional annotation techniques reaction small molecule similarity. Turning engineering, discuss strategies thermostability, solubility, activity, well applications AI these fields. The shift from traditional experiment‐driven data‐driven computationally driven is already underway. Finally, present potential provide perspective future research directions. envision expanded biocatalysis drug development, green chemistry, complex synthesis.

Язык: Английский

Engineered Proteins and Chemical Tools to Probe the Cell Surface Proteome

Chemical Reviews, Год журнала: 2025, Номер unknown

Опубликована: Апрель 3, 2025

The cell surface proteome, or surfaceome, is the hub for cells to interact and communicate with outside world. Many disease-associated changes are hard-wired within yet approved drugs target less than 50 proteins. In past decade, proteomics community has made significant strides in developing new technologies tailored studying surfaceome all its complexity. this review, we first dive into unique characteristics functions of emphasizing necessity specialized labeling, enrichment, proteomic approaches. An overview surfaceomics methods provided, detailing techniques measure protein expression how leads novel discovery. Next, highlight advances proximity labeling (PLP), showcasing various enzymatic photoaffinity can map protein-protein interactions membrane complexes on surface. We then review role extracellular post-translational modifications, focusing glycosylation, proteolytic remodeling, secretome. Finally, discuss identifying tumor-specific peptide MHC they have shaped therapeutic development. This emerging field neo-protein epitopes constantly evolving, where targets identified at proteome level encompass defined PTMs, complexes, dysregulated cellular tissue locations. Given functional importance biology therapy, view as a critical piece quest neo-epitope

Язык: Английский