Investigation of the binding preference of reovirus sigma1 for junctional adhesion molecule A by classical and steered molecular dynamics.

Biochemical studies have determined that reoviruses attach to cells by combining attachment protein sigma1 to the binding interface of its receptor protein junctional adhesion molecule A (JAM-A), and the interface normally takes care of the homodimerization of JAM-A. Tighter binding and slower dissociation of for the sigma1-JAM complex than for the JAM-JAM complex have been probed by both biological and atomic force microscopy experiments; however, the mechanism of the binding preference of the attachment protein for JAM-A still remains unclear. With the help of classical and steered molecular dynamics and energy calculations, the unbinding forces and kinetic properties of the complexes are investigated, together with detailed structural information analyses. A multireceptor mechanism is proposed for the binding preference, which can be helpful for future viral infection and vector targeting studies.