|
Proteins are polyatomic molecules and, as such, their physico-chemical properties are largely determined by the distribution of electronic charge throughout their complex 3D structures. For instance, it is well established that the elctrostatic potential plays an important role in the formation of protein-protein and protein-DNA complexes via molecular recognition. However, proteins are subject to conformational changes which do affect their biological activities both in vivo and in vitro. Hence, we may ask what is the relationship between electronic structure and protein dynamics? We have been trying to answer such question by investigating ensembles of protein conformers with the aid of quantum mechanical calculations [1]. The first ensemble investigated by us is the DER ensemble of 128 ubiquitin conformers which has been recently determined by NMR spectroscopy [2]. Our calculations indicate that properties such as the macrodipole do fluctuate within a range of about 150 Debye whereas the localization of the frontier orbitals of the protein is not effected by its dynamics. These results have interesting implications for the biochemistry of ubiquitination, a post-translational modification that is concerned with signaling events inside the cell. A second ensemble of 116 ubiquitin conformers, the EROS ensemble, has also been determined by NMR spectroscopy and is claimed to sample those conformers which are concerned with the recognition properties of this protein [3]. For the first time, our analysis of these conformational ensembles has shed light on the intimate relationship between protein dynamics and electronic structure.
[1] F. Pichierri, Chem. Phys. Lett. 410 (2005) 462. [2] K. Lindorff-Larsen et al., Nature 433 (2005) 128. [3] O.F. Lange et al., Science 320 (2008) 1471. |
|