Thermodynamics of Protein Hydration Computed by Molecular Dynamics and Normal Modes

Abstract

Thermodynamic properties of bovine pancreatic trypsin inhibitor (BPTI) hydrated by up to 1600 water molecules, i.e., a ratio of the weight of water to that of protein, h, from 0 to ∼4.5, are studied by molecular dynamics (MD) simulation and normal-mode analysis (NMA). Temperatures range from 100 to 300 K to include the hydrated protein glass transition, Tg ≈ 200 K. The partial specific heat of BPTI computed by MD reaches fully hydrated values around h ≈ 0.7 below and above Tg. For smaller h, distinctly different variations in the apparent specific heat of BPTI with h below and above Tg are found and related to the respective decrease and increase in protein flexibility with h. Changes upon varying h in the energy landscape of hydrated BPTI near its native configuration are examined. The partial entropy of BPTI is computed with NMA up to Tg. Above 200 K, an increase in the partial entropy of BPTI is computed with specific heats of hydrated BPTI obtained by MD. The difference between the partial entropy of ...