Unveiling the adaptive structure-function synergy in thermophilic translation initiation factor 1: A molecular...

The translation mechanism in thermophilic bacteria requires unique adaptations to maintain its efficiency under extreme temperatures. Stabilised ribosomal interactions and recognition of the start codon are facilitated by Initiation Factor 1 (IF1). However, the underlying atomistic foundation behind its thermal resilience is not yet fully elucidated. In this study, we performed comprehensive molecular dynamics simulations (1000 ns each, in triplicate) to evaluate the dynamic properties of IF1 from the thermophilic bacterium Thermoanaerobacterium thermosaccharolyticum (TT_IF1) compared to its mesophilic counterpart (FK_IF1, IF1 from Flavobacterium kingsejongi). Our analyses point to enhanced structural rigidity in TT_IF1, stabilised by an expanded network of hydrogen bonds and salt bridges. Principal component analysis highlighted restricted conformational fluctuations, suggesting evolutionary optimisation to minimise entropy-driven destabilisation at elevated temperatures. Furthermore, residue-level flexibility profiles indicated that TT_IF1 maintains a delicate balance between stability and functional plasticity, preserving its ability to interact with ribosomal RNA while resisting thermal unfolding. These findings provide mechanistic insights into the molecular strategies underlying thermophilic adaptation of translation initiation factors. Beyond fundamental biology, this work establishes a framework for engineering thermostable protein variants with potential applications in synthetic biology and industrial biotechnology.