Hybrid Modeling Approaches to Study Structures and Dynamics of Biological Systems

Abstract

Determination of the structure and dynamics of large biological complexes can be performed using experimental techniques ranging from high to low-resolution. With recent progress in experimental techniques, raw data from Cryo Electron Microscopy (cryo-EM) may now comprise millions of two-dimensional (2D) images of single molecules. These may represent distinct conformations of the molecule; therefore, dynamics information might also be embedded within the 2D data. X-ray free electron laser (XFEL) is another exciting new technology that could significantly extend our structural knowledge of biological systems. Strong laser light from XFEL enables the measurement of single molecular complex, without necessity of crystallization. However, for biological systems, due to their low diffraction power, interpretation of the data remains challenging. Given progresses in experimental techniques, new computational methods are needed to process and interpret data obtained from these single particle experiments. We will discuss hybrid computational methods that combine molecular mechanics and image data processing algorithms to derive structural and dynamical information from cryo-EM and XFEL data.