General Physics Colloquium, Professor Nozomi Ando, Department of Chemistry & Chemical Biology, Cornell University

Title:  Beyond Bragg Diffraction:  Toward the Next Century of Structural Biology

Host:  Nigel Lockyer

Abstract:  Over the past seventy years, structural biology has produced more than 250,000 atomic models of proteins. These structures have transformed medicine, biotechnology, and now artificial intelligence. This success rests largely on X-ray crystallography and the measurement of Bragg diffraction — sharp reflections arising from crystalline periodicity that report the average electron density of the unit cell, the repeating motif of the crystal. However, Bragg diffraction captures only part of the scattered intensity. A comparable number of photons sample all of reciprocal space, forming diffuse scattering patterns that arise from unit cell-to-unit-cell variability and encode spatial correlations not found in Bragg diffraction. In this talk, I will describe our efforts to extract and understand this signal, leveraging advances in detector technology to reconstruct three-dimensional maps of reciprocal space with sufficient fidelity to test physical models of lattice dynamics and molecular motion. I will also discuss how this work led to Project Diffuse, a recently initiated multi-institution initiative supported by philanthropic funding to build the infrastructure needed to make diffuse scattering broadly accessible. Our long-term goal is not merely to improve crystallography but to generate experimentally validated models of protein dynamics and ultimately to help establish a future of structural biology in which we not only share static average structures, but also quantitative information about structural motion.