Title:	SeMet - Heavy Atom Markers for Protein Orientation Determination
DNr:	NAISS 2025/22-1019
Project Type:	NAISS Small Compute
Principal Investigator:	Xinyue Gao <xinyue.gao@kemi.uu.se>
Affiliation:	Uppsala universitet
Duration:	2025-07-31 – 2026-08-01
Classification:	10408
Keywords:

Abstract

Single-particle imaging has proven as a significant way to determine the structure of proteins, however, detecting the orientation of proteins remains an unsolved problem that complicates structure determination. An introduction of heavier atoms into the proteins can be an indicator of orientation, either via their contribution to the scattered X-rays, or via their explosion trajectories post-exposure in velocity map imaging. We focus specifically on selenomethionine, a methionine analog where selenium replaces sulfur, offering an optimal balance between detectability in diffraction patterns and biological compatibility—a modification extensively utilized in protein crystallography. We will begin with lysozyme as a model system, conducting comprehensive simulations in both solution and gas-phase environments to establish baseline parameters and validate our computational protocols. Then we will extend to larger protein systems and explore alternative heavy atom incorporation strategies to optimize orientation detection capabilities.