Title: A practical guide to the simultaneous determination of protein structure and dynamics using metainference,
Abstract: Accurate protein structural ensembles can be determined with metainference, a
Bayesian inference method that integrates experimental information with prior
knowledge of the system and deals with all sources of uncertainty and errors as
well as with system heterogeneity. Furthermore, metainference can be
implemented using the metadynamics approach, which enables the computational
study of complex biological systems requiring extensive conformational
sampling. In this chapter, we provide a step-by-step guide to perform and
analyse metadynamic metainference simulations using the ISDB module of the
open-source PLUMED library, as well as a series of practical tips to avoid
common mistakes. Specifically, we will guide the reader in the process of
learning how to model the structural ensemble of a small disordered peptide by
combining state-of-the-art molecular mechanics force fields with nuclear
magnetic resonance data, including chemical shifts, scalar couplings and
residual dipolar couplings.