Paper Citing NAMD - Abstract
Pan, Di; Song, Yuhua
Effects of Altered Restraints in beta 1 Integrin on the Force-Regulated Interaction between the Glycosylated I-Like Domain of beta 1 Integrin and Fibronectin III9-10: A Steered Molecular Dynamic Study
Molecular & Cellular Biomechanics, 8:233-252, SEP 2011
Cytoskeletal restraints affect force-regulated integrin function in cell adhesion. However, the structural and molecular basis underlying the effect of cytoskeletal restraints on beta 1 integrin binding to fibronectin is still largely unknown. In this study, we used steered molecular dynamics simulations to investigate the changes in glycosylated beta 1 integrin-fibronectin binding and in conformation and structure of the glycosylated beta 1 I-like domain-FN-III9-10 complex caused by altered restraints applied to beta 1 I-like domain. The results revealed that imposition of the increased constraints on beta 1 integrin increased resistance to force-induced dissociation of the beta 1 I-like domain-fibronectin complex. Specifically, the increased constraints enhanced resistance to relative conformational changes in the RGD-synergy site in fibronectin, increased the conformational stability of fibronectin, and prevented losses in hydrogen bond occupancy of each beta-strand pair in FN-III10 resulting from external force. The increased constraints also resulted in an increase in correlated motion between residues in the beta 1 I-like domain, which may directly affect the interaction of beta 1 integrin with fibronectin. Results from this study provide molecular and structural insights into the effects of altered restraints in beta 1 integrin on the interaction between glycosylated beta 1 Integrin and fibronectin and its induced cell adhesion.
