Abstract
The interplay of three biomolecules, DNA, RNA and proteins provide complexity and richness to the biological world. Proteins have long been the primary research focus among various groups across the world. The nature of their internal dynamics, apart from the biochemical and functional aspects, has attracted enormous attention. Investigation of the factors governing the dynamics can give valuable insights into protein activity or functions. Advanced theoretical and experimental techniques contribute to the better understanding of protein structures, stabilities and internal dynamics. Computer simulations provide with an excellent alternative to interpret and complement the experimental investigations and provide a molecular level insight into protein structure, dynamics and functions. This atomistic-level information obtained from biomolecular simulations can be used to derive various experimentally measurable macroscopic observables, including heat capacity, free energy, by using statistical mechanics.
Like harmonic solids, the protein atoms execute harmonic vibrations around their equilibrium positions, at low temperatures. Upon heating, the amplitude of these harmonic motions increases linearly with the increase in temperature up to a critical temperature (Tg) beyond which a transition from the glass-like phase to liquid-like phase is observed. Atomistic MD simulations calculate dynamical properties relevant to harmonic-to-anharmonic transition which are attributed to flexibility in proteins and onset of biological activity. The glass transitions have been reported in proteins, DNA and RNA by various experimental and simulation studies. The glass-transition temperature (Tg) is observed at about 220 K. Recently, a low-temperature anharmonic transition has been observed in many proteins at around 150 K, that is much below the Tg. Reasons for the same have not clearly been stated. This work is an attempt to understand the underlying factors which contribute significantly to this behavior.
The present work emphasizes on the role of MD simulations to understand the factors that contribute to the anharmonic transitions of proteins. Four homomeric polypeptides, polyglycine, polyalanine, polyisoleucine and polyphenylalanine have been analyzed for the dynamical behavior of each kind of side-chains to the anharmonic transitions over a range of temperatures (between 10K and 300K in steps of 10K). The dynamical properties of proteins are largely attributed to the amino acid side-chain groups as is exemplified by the system under consideration. Polyglycine, representing backbone-only polypeptide shows only solvent-dependent dynamical transition, while as polyalanine, polyisoleucine and polyphenylalanine shows a low-temperature onset of anharmonicity along with the dynamical transition at the critical temperature (Tg). The results obtained from our simulation studies correspond exactly with the experimental data from elastic incoherent neutron scattering (EINS) studies.