Forum 04/29/2004

“Visualization by cryo-EM and analysis of the molecular dynamics of herpes simplex virus capsid maturation”

Bernard Heymann – Image Processing Specialist, Caltech

Cryo-electron microscopy of single particles offers a unique opportunity to detect and quantify conformational changes of protein complexes. In one such study, the large-scale structural changes of the herpes simplex virus type 1 (HSV1) capsid as it matures from the initial spherical procapsid to the final mature capsid were captured by time-resolved cryo-electron microscopy. The different conformers were reconstructed from a 3D classification of particle images along the time course of in vitro capsid maturation, i.e., “multiple particle analysis” – MPA. The transformation of the capsid shows one major switch, preceded and followed by many smaller structural modifications. The spontaneous nature of the process suggests that the driving force for maturation is geometric, a notion that can be tested by simplified molecular dynamics. In addition, the classification of the particles in MPA provides conformational distributions amenable to kinetic analysis.

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