biostudies-literatureChen MNIMHNIMH NIH HHSNational Institutes of HealthNIGMS NIH HHSAir Force Office of Scientific ResearchNIGMS168014https://www.ebi.ac.uk/biostudies/studies/S-EPMC10164680biostudies-literatureUnknown435(9)Resolving the structural variability of proteins is often key to understanding the structure-function relationship of those macromolecular machines. Single particle analysis using Cryogenic electron microscopy (CryoEM), combined with machine learning algorithms, provides a way to reveal the dynamics within the protein system from noisy micrographs. Here, we introduce an improved computational method that uses Gaussian mixture models for protein structure representation and deep neural networks for conformation space embedding. By integrating information from molecular models into the heterogeneity analysis, we can analyze continuous protein conformational changes using structural information at the frequency of 1/3 Å^-1, and present the results in a more interpretable form.Journal of molecular biologyIntegrating Molecular Models Into CryoEM Heterogeneity Analysis Using Scalable High-resolution Deep Gaussian Mixture Models.PMC10164680FA9550-21-1-0317R01 GM136780R21MH125285R21 MH125285R01GM136780R01 GM080139R01GM080139Toader BChen MLederman RfalseIntegrating Molecular Models Into CryoEM Heterogeneity Analysis Using Scalable High-resolution Deep Gaussian Mixture Models.Resolving the structural variability of proteins is often key to understanding the structure-function relationship of those macromolecular machines. Single particle analysis using Cryogenic electron microscopy (CryoEM), combined with machine learning algorithms, provides a way to reveal the dynamics within the protein system from noisy micrographs. Here, we introduce an improved computational method that uses Gaussian mixture models for protein structure representation and deep neural networks for conformation space embedding. By integrating information from molecular models into the heterogeneity analysis, we can analyze continuous protein conformational changes using structural information at the frequency of 1/3 Å^-1, and present the results in a more interpretable form.2023-01-01T00:00:00Z2023 May2026-06-01T23:49:59.442Z2026-05-23T03:08:11.175ZS-EPMC101646803680647610.1016/j.jmb.2023.168014