Dynamic Coupling and Entropy Changes in KRAS G12D Mutation: Insights into Molecular Flexibility, Allostery and Function.

The oncogenic G12D mutation in KRAS is a major driver of cancer progression, yet the complete mechanism by which this mutation alters protein dynamics and function remains incompletely understood. Here, we investigate how the G12D mutation alters KRAS's conformational landscape and residue-residue interactions using molecular dynamics simulations coupled with entropy calculations and mutual information (MI) analysis. We demonstrate that the mutation increases local entropy at key functional residues (D12, Y32, G60, and Q61), and introduces new peaks to the Ramachandran angles, disrupting the precise structural alignment necessary for GTP hydrolysis.

Mode coupling points to functionally important residues in myosin II.

Relevance of mode coupling to energy/information transfer during protein function, particularly in the context of allosteric interactions is widely accepted. However, existing evidence in favor of this hypothesis comes essentially from model systems. We here report a novel formal analysis of the near-native dynamics of myosin II, which allows us to explore the impact of the interaction between possibly non-Gaussian vibrational modes on fluctutational dynamics.

Quantum mechanical calculations of tryptophan and comparison with conformations in native proteins.

We report a detailed analysis of the potential energy surface of N-acetyl-l-tryptophan-N-methylamide, (NATMA) both in the gas phase and in solution. The minima are identified using the density-functional-theory (DFT) with the 6-31g(d) basis set. The full potential energy surface in terms of torsional angles is spanned starting from various initial configurations.