Biomedical Engineering Reference
In-Depth Information
Chapter 1
Towards a Coarse-Grained Model for Unfolded
Proteins
Ali Ghavami, Erik Van der Giessen, and Patrick R. Onck
Abstract
It is widely accepted that many biological systems benefit from the spe-
cific and unique properties of unfolded proteins. In order to study the conformational
dynamics of these proteins, we propose an implicit solvent one-bead per amino-acid
coarse-grained (CG) model. For the local backbone interactions, experimentally-
obtained Ramachandran plots for the coil regions of proteins are converted into dis-
tributions of pseudo-bond and pseudo-dihedral angles between neighboring alpha-
carbons in the CG chain. The obtained density plots are then used to derive bending
and torsion potentials, which are residue- and sequence-specific. Our results show
that the local interactions can be captured by specifically accounting for the pres-
ence of Proline and Glycine in the amino-acid sequence. An upper and lower bound
is suggested for the radius of gyration of denatured proteins based on their specific
sequence composition.
1.1 Introduction
In spite of the well-established relation between the biological function of proteins
and their specific folded structure, the important role of unfolded proteins in many
vital biological processes can not be ignored (Fink,
2005
; Tompa,
2009
). Rapid
increase of our knowledge on the structure of proteins has revealed that many pro-
teins and protein domains are intrinsically unstructured. The absence of a stable
secondary structure in their polypeptide chain is the main reason behind the basic
functions of unfolded proteins, which can be classified into four functional groups,
namely molecular recognition, molecular assembly, protein modification and en-
tropic chain activities (Dunker et al.,
2002
; Radivojac et al.,
2007
; Tompa,
2009
).
Atomic-level molecular dynamics simulations provide detailed insight of the
interactions and dynamics present in protein structures. However, because of the
limitations in computational resources it is still not possible to reach biologically-
interesting time and length scales. Unfolded proteins are even more dynamic and
A. Ghavami
·
E. Van der Giessen
·
P. R . O n c k (
)
Zernike Institute for Advanced Materials, University of Groningen, Groningen, The Netherlands
e-mail:
p.r.onck@rug.nl
