Echo dephasing and heat capacity from constrained and unconstrained dynamics of triiodothyronine nuclear receptor...

The objective of this study is to observe the echo feature curves, vibrational dephasing, and heat capacity of a protein-hormone system taking thyroid hormone receptor-beta (THR-β) as an example. Constrained and unconstrained molecular dynamics simulations are performed by implementing the theory of velocity reassignments to probe the phase coherent state in terms of echo pulses. The constrained vibrations are incorporated by adjusting rigid bonds to all hydrogen atoms with an integrator parameter of 2 fs/step in order to reduce the degrees of freedom whereas 1 fs/step is used in the free vibrations of the atomic cluster. The nature of temperature auto-correlation functions changes so that echo feature curves also show a distinct nature in the cases of constrained and unconstrained vibrations. There is a large variation in kinetic temperature and internal potential energy in the echo time zone. The temperature rate of change of internal potential energy is the main contributor to the heat capacity of the native state protein-hormone system. The heat capacity of proteins estimated from this technique is in good agreement with the values from experiments. This study shows that triiodothyronine (T3) hormone makes some differences in heat capacity upon binding to the THR-β ligand binding domain (LBD). The physical properties of unliganded THR-β and T3-bound THR-β LBD in the cases of constrained and unconstrained dynamics are observed distinctly under the effect of anharmonicity on the phase coherent state of normal modes and the dephasing time lies in a range of 0.6-0.8 ps when the systems are perturbed suddenly.