Marc Aurèle Gilles

Marc Aurèle Gilles, Alex Townsend

Analogues of the conjugate gradient method, MINRES, and GMRES are derived for solving boundary value problems (BVPs) involving second-order differential operators. Two challenges arise: imposing the boundary conditions on the solution while building up a Krylov subspace, and guaranteeing convergence of the Krylov-based method on unbounded operators. Our approach employs projection operators to guarantee that the boundary conditions are satisfied, and we develop an operator preconditioner that ensures that an approximate solution is computed after a finite number of iterations. The developed Krylov methods are practical iterative BVP solvers that are particularly efficient when a fast operator-function product is available.

Marc Aurèle Gilles, Amit Singer

Background and Objective: Wilson statistics describe well the power spectrum of proteins at high frequencies. Therefore, it has found several applications in structural biology, e.g., it is the basis for sharpening steps used in cryogenic electron microscopy (cryo-EM). A recent paper gave the first rigorous proof of Wilson statistics based on a formalism of Wilson's original argument. This new analysis also leads to statistical estimates of the scattering potential of proteins that reveal a correlation between neighboring Fourier coefficients. Here we exploit these estimates to craft a novel prior that can be used for Bayesian inference of molecular structures. Methods: We describe the properties of the prior and the computation of its hyperparameters. We then evaluate the prior on two synthetic linear inverse problems, and compare against a popular prior in cryo-EM reconstruction at a range of SNRs. Results: We show that the new prior effectively suppresses noise and fills-in low SNR regions in the spectral domain. Furthermore, it improves the resolution of estimates on the problems considered for a wide range of SNR and produces Fourier Shell Correlation curves that are insensitive to masking effects. Conclusions: We analyze the assumptions in the model, discuss relations to other regularization strategies, and postulate on potential implications for structure determination in cryo-EM.