Hui Lu and Klaus Schulten.
Steered molecular dynamics simulation of conformational changes of
immunoglobulin domain I27 interpret atomic force microscopy observations.
Chemical Physics, 247:141-153, 1999.
LU99AAtomic force microscopy and steered molecular dynamics investigations of the response of so-called mechanical proteins like titin, tenascin or their individual immunoglobin and fibronectin domains have lead to qualitative insights about the relationship between sandwich domain architecture and the function of this class of proteins. The proteins, linear segments of up to hundreds of domains, through strain induced shape changes, unfolding and refolding, maintain order and elasticity in cellular systems over a nearly tenfold length scale. In this paper we develop a steered molecular dynamics description of the response of the immunoglobulin domain I27 at the onset of domain unfolding in quantitative agreement with AFM observations. We show that if forces stronger than 50 pN are applied between the terminal ends, the two hydrogen bonds between the antiparallel A a B strands break with a concomitant 6 elongation of the protein. If forces strong enough to unfold the domain are applied, the protein is halted in this initial extension until the set of all six hydrogen bonds connecting strands A' and G break simultaneously. This behavior is accounted for by a barrier separating folded states, the shape of which is consistent with AFM and denaturation data. We also demonstrate that steered molecular dynamics simulations which induce unfolding through slow pulling (speed 0.1 /ps) predict unfolding forces that are within a factor of two within force values extrapolated from AFM observations.
This document was last
modified on Fri Oct 11 10:32:21 2002
Material on this page is copyrighted
Contact Webmaster for
more information
148124 accesses since 03 Nov 2000
sandwich domain architecture and the function of this class of proteins. The proteins, linear segments of up to hundreds of domains, through strain induced shape changes, unfolding and refolding, maintain order and elasticity in cellular systems over a nearly tenfold length scale. In this paper we develop a steered molecular dynamics description of the response of the immunoglobulin domain I27 at the onset of domain unfolding in quantitative agreement with AFM observations. We show that if forces stronger than 50 pN are applied between the terminal ends, the two hydrogen bonds between the antiparallel A a B 
elongation of the protein. If forces strong enough to unfold the domain are applied, the protein is halted in this initial extension until the set of all six hydrogen bonds connecting strands A' and G break simultaneously. This behavior is accounted for by a barrier separating folded states, the shape of which is consistent with AFM and denaturation data. We also demonstrate that steered molecular dynamics simulations which induce unfolding through slow pulling (speed 0.1