  The assembly of proteins in membranes plays a key role in many crucial
cellular pathways. Despite their importance, characterizing transmembrane
assembly remains challenging for experiments and simulations. Equilibrium
molecular dynamics simulations do not cover the time scales required to sample
the typical transmembrane assembly. Hence, most studies rely on enhanced
sampling schemes that steer the dynamics of transmembrane proteins along a
collective variable that should encode all slow degrees of freedom. However,
given the complexity of the condensed-phase lipid environment, this is far from
trivial, with the consequence that free energy profiles of dimerization can be
poorly converged. Here, we introduce an alternative approach, which relies only
on simulating short, dynamically unbiased trajectory segments, avoiding using
collective variables or biasing forces. By merging all trajectories, we obtain
free energy profiles, rates, and mechanisms of transmembrane dimerization with
the same set of simulations. We showcase our algorithm by sampling the
spontaneous association and dissociation of a transmembrane protein in a lipid
bilayer, the popular coarse-grained Martini force field. Our algorithm
represents a promising way to investigate assembly processes in biologically
relevant membranes, overcoming some of the challenges of conventional methods.
