TY  - JOUR
AU  - Yorke, Briony A.
AU  - Ginn, Helen
TI  - Calculation of minimum energy pathways in transport proteins
JO  - Communications chemistry
VL  - 8
IS  - 1
SN  - 2399-3669
CY  - [London]
PB  - Macmillan Publishers Limited, part of Springer Nature
M1  - PUBDB-2026-00028
SP  - 377
PY  - 2025
N1  - cc-by
AB  - Although static structures of protein metastable states are well-studied, the fleeting transitions between these states are difficult to experimentally observe or predict. We present a computationally inexpensive algorithm, “cold-inbetweening”, which generates trajectories between experimentally determined end-states. Here we apply cold-inbetweening to provide mechanistic insight into the ubiquitous alternate access model of operation in three membrane transporter superfamilies. Here, we study DraNramp from Deinococcus radiodurans, MalT from Bacillus cereus, and MATE from Pyrococcus furiosus. In MalT, the trajectory demonstrates elevator transport through unwinding of a supporter arm helix, maintaining adequate space to transport maltose. In DraNramp, outward-gate closure occurs prior to inward-gate opening, in accordance with the alternate access hypothesis. In the MATE transporter, switching conformation involves obligatory rewinding of the N-terminal helix to avoid steric backbone clashes. This concurrently plugs the cavernous ligand-binding site mid-conformational change. Cold-inbetweening can generate hypotheses about large functionally relevant protein conformational changes.
LB  - PUB:(DE-HGF)16
DO  - DOI:10.1038/s42004-025-01754-1
UR  - https://bib-pubdb1.desy.de/record/643130
ER  -