Achieving broad molecular insights into dynamic protein interactions by integrated structural–kinetic approaches

A network of dynamic protein interactions with their protein partners, substrates, and ligands is known to be crucial for biological function. Revealing molecular and structural-based mechanisms at atomic resolution and in real-time is fundamental for achieving a basic understanding of cellular processes. These technically challenging goals may be achieved by combining time-resolved spectroscopic and structural–kinetic tools, thus providing broad insights into specific molecular events over a wide range of timescales. Here we review representative studies utilizing such an integrated real-time structural approach designed to reveal molecular mechanisms underlying protein interactions at atomic resolution.

► Revealing molecular mechanisms governing dynamic protein interactions is crucial for understanding protein function. ► Although technically challenging, generating detailed structural–dynamic models of protein interactions is highly desired. ► We review studies utilizing novel integrated real-time structural experiments designed to reveal protein molecular mechanisms. ► This emerging experimental approach provides high-level structure based mechanistic information on protein function.