Speakers
Description
In this work, we address the continuous heterogeneity problem. We parametrize the 3D density maps of the particles being imaged using a low-dimensional manifold of conformations. This parametrization is based on low-resolution reconstructions and Laplacian eigenmaps. We use this parametrization to form a generalized tomographic reconstruction problem which reconstructs a density map at each point on the manifold. The resulting set of equations is high-dimensional, but by exploiting certain properties we recast the problem as a deconvolution. It can be solved efficiently using the conjugate gradient method, where the forward operator kernel is calculated non-uniform FFT. The solution of this problem is given by a set of spectral volumes. These volumes are used to calculate high-resolution reconstructions of the projected particles as well as providing insight into the nature of the conformational changes. We present results for this method on both simulated models and experimental data.
