Laboratory for Dynamic Biomolecule Design

Membrane proteins are key molecules that transport ions and small molecules and trigger signal transduction at cell membranes. These functions are realised through protein folding of their linear amino acid sequences into three-dimensional structures and, most importantly, through their dynamic structural changes. However, capturing the accurate structural dynamics of membrane proteins, particularly, remains challenging due to their broad, hierarchical spatio-temporal scales and another dynamic factor, the lipid bilayers. Our team adopts a bottom-up approach using rationally designed proteins to address the question: how do protein structural dynamics contribute within the context of biological functions? Our ultimate goal is to elucidate the molecular mechanisms, especially of neuronal and immune signal transduction.

As a research outcome this year, we reported amino acid sequence design rules that precisely control the association number of artificially designed peptide channels to 5, 6, or 7, achieved through computational design. Furthermore, we discovered that these peptide channels undergo voltage-dependent structural changes through single-channel current recordings. Combining these experimental findings with molecular dynamics simulations under external electric fields, we proposed the underlying molecular mechanism of the kinetic structural dynamics. This achievement is anticipated to lead to the bottom-up design of voltage-gated ion channels and, ultimately, the reconstruction of neural signal transduction systems.

Also, in our first year at IMS, we started several collaborations within the centre. We will actively seek further opportunities to apply designed proteins to life and medical science within IMS.