  Protein function and activity are a consequence of its three-dimensional
structure. Single particle analysis of cryogenic electron micrographs has
radically changed structural biology allowing atomic reconstruction of almost
any type of proteins. While such an approach provides snapshots of
three-dimensional structural information that can be correlated with function,
the new frontier of protein structural biology is in the fourth dimension,
time. Here we propose the use of liquid phase electron microscopy to expand
structural biology into dynamic studies. We apply here single particle analysis
algorithm to images of proteins in Brownian motion through time; thus, Brownian
single particle analysis (BSPA). BSPA enables to reduce the acquisition time
from hours, in cryo-EM, to seconds and achieve information on conformational
changes, hydration dynamics, and effects of thermal fluctuations. Yielding all
these previously neglected aspects, BSPA may lead to the verge of a new field:
dynamic structural biology.
