Ab-initio simulations of metallo-proteins: structure, dynamics and XAS spectra

We propose to study the structure and dynamics of two metalloproteins: cytochrome c (cyt c) and carboxymyoglobin (MbCO) using DFT ab-initio simulations. The objective is to study their equilibrium structure and the vibrational dynamics in order to gain insight in recently detected matrix effects. In fact, in an experimental investigation using X-ray absorption spectroscopy (XAS), some of us have found [1] that a strongly dehydrated trehalose matrix hinders the protein’s local dynamics and induces strong changes in the atomic environment around the metal atoms. Trehalose is a disaccharide found in nature in many organisms that can undergo unhydrobiosis, a condition that allows them to preserve their structural integrity and functionality over years of dehydration, and which is thus considered to have a bioprotectant action. A present limitation of the analysis of the XAS data is that there is little knowledge of the Debye-Waller factors (DW), for which ad-hoc assumptions are usually made; we believe that ab-initio simulation will provide crucial input on the expected values of DWs and a sound framework within which to interpret the experimental data. This kind of joint theoretical – simulation investigation has, in our opinion, a more general interest since the method can be applied to a numerous class of problems. There is great interest in this issue in the scientific community, as testified by recent publications. While earlier approaches rely on the solution of the equations of motion using external force constants as inputs [2], ab-initio simulations have been used by one group for Zn metalloproteins [3].