MOTIVATION: Therapeutic antibodies have emerged as a prominent class of new drugs due to their high specificity and their ability to bind to several protein targets. Once an initial antibody has been identified, its design and characteristics are refined using structural information, when it is available. Cryo-EM is currently the most effective method to obtain 3D structures. It relies on well-established methods to process raw data into a 3D map, which may, however, be noisy and contain artifacts. To fully interpret these maps the number, position, and structure of antibodies and other proteins present must be determined. Unfortunately, existing automated methods addressing this step have limited accuracy, require additional inputs and high-resolution maps, and exhibit long running times. RESULTS: We propose the first fully automatic and efficient method dedicated to finding antibodies in cryo-EM maps: CrAI. This machine learning approach leverages the conserved structure of antibodies and a dedicated novel database that we built to solve this problem. Running a prediction takes only a few seconds, instead of hours, and requires nothing but the cryo-EM map, seamlessly integrating within automated analysis pipelines. Our method can find the location and pose of both Fabs and VHHs at resolutions up to 10 Å and is significantly more reliable than existing approaches. AVAILABILITY AND IMPLEMENTATION: We make our method available both in open source github.com/Sanofi-Public/crai and as a ChimeraX bundle (crai).

MOTIVATION: A protein can be represented in several forms, including its 1D sequence, 3D atom coordinates, and molecular surface. A protein surface contains rich structural and chemical features directly related to the protein's function such as its ability to interact with other molecules. While many methods have been developed for comparing the similarity of proteins using the sequence and structural representations, computational methods based on molecular surface representation are limited. RESULTS: Here, we describe "Surface ID," a geometric deep learning system for high-throughput surface comparison based on geometric and chemical features. Surface ID offers a novel grouping and alignment algorithm useful for clustering proteins by function, visualization, and in silico screening of potential binding partners to a target molecule. Our method demonstrates top performance in surface similarity assessment, indicating great potential for protein functional annotation, a major need in protein engineering and therapeutic design. AVAILABILITY AND IMPLEMENTATION: Source code for the Surface ID model, trained weights, and inference script are available at https://github.com/Sanofi-Public/LMR-SurfaceID.