article published yes Petar N Petrov author b1d6732d-8cb6-11f0-baab-bd460ee3a287 Jessie T. Zhang author Jonathan Remis author Jeremy J. Axelrod author Hang Cheng author Eric S. Cooper author Ian K. Hicklin author Shahar Sandhaus author Cooper Schnurr author Robert M. Glaeser author Holger Müller author MiLe department Phase plates can, in principle, overcome the poor image contrast in cryo–electron microscopy (cryo-EM) and the resulting limits on the structural reconstruction of small proteins. However, previous designs have been unstable and compromised the high-resolution signal and have thus been unable to surpass results achieved by standard cryo-EM. Here, we show that the laser phase plate (LPP), installed in a modern, custom Titan Krios microscope, enhances the resolution in single-particle reconstruction of small proteins by improving specimen-motion correction and recovery of information from the early frames, as well as particle visualization, three-dimensional classification, and alignment. These advances use standard defocus ranges and reconstruction procedures but open the door to LPP-tailored protocols, offering further improvements by leveraging the LPP demonstrated here. AAAS2026 eng 0036-8075 1095-9203 4227546610.1126/science.aeh0665 3936807195-196 Petrov PN, Zhang JT, Remis J, et al. Laser phase plate improves structure determination of small proteins by cryo-EM. <i>Science</i>. 2026;393(6807):195-196. doi:<a href="https://doi.org/10.1126/science.aeh0665">10.1126/science.aeh0665</a> Petrov PN, Zhang JT, Remis J, Axelrod JJ, Cheng H, Cooper ES, Hicklin IK, Sandhaus S, Schnurr C, Glaeser RM, Müller H. 2026. Laser phase plate improves structure determination of small proteins by cryo-EM. Science. 393(6807), 195–196. P.N. Petrov, J.T. Zhang, J. Remis, J.J. Axelrod, H. Cheng, E.S. Cooper, I.K. Hicklin, S. Sandhaus, C. Schnurr, R.M. Glaeser, H. Müller, Science 393 (2026) 195–196. Petrov, P. N., Zhang, J. T., Remis, J., Axelrod, J. J., Cheng, H., Cooper, E. S., … Müller, H. (2026). Laser phase plate improves structure determination of small proteins by cryo-EM. <i>Science</i>. AAAS. <a href="https://doi.org/10.1126/science.aeh0665">https://doi.org/10.1126/science.aeh0665</a> Petrov, Petar N, Jessie T. Zhang, Jonathan Remis, Jeremy J. Axelrod, Hang Cheng, Eric S. Cooper, Ian K. Hicklin, et al. “Laser Phase Plate Improves Structure Determination of Small Proteins by Cryo-EM.” <i>Science</i>. AAAS, 2026. <a href="https://doi.org/10.1126/science.aeh0665">https://doi.org/10.1126/science.aeh0665</a>. Petrov, Petar N., et al. “Laser Phase Plate Improves Structure Determination of Small Proteins by Cryo-EM.” <i>Science</i>, vol. 393, no. 6807, AAAS, 2026, pp. 195–96, doi:<a href="https://doi.org/10.1126/science.aeh0665">10.1126/science.aeh0665</a>. P. N. Petrov <i>et al.</i>, “Laser phase plate improves structure determination of small proteins by cryo-EM,” <i>Science</i>, vol. 393, no. 6807. AAAS, pp. 195–196, 2026. 223652026-07-19T22:01:46Z2026-07-20T12:58:46Z