Atomic modeling of an immature retroviral lattice using molecular dynamics and mutagenesis


Retroviruses are parasites that pose a major health threat to humans (for example in case of HIV) and other animals (for example in case of RSV, M-PMV, MLV, and many more viruses). After a retrovirus hijacks a cell, the infected cell produces multiple copies of the virus which are then released into the host's bloodstream. These newly released viruses must mature before they can infect other cells. A strategy for preventing virus spread is therefore, to lock the viral particles in their immature, non-infectious state. However, to render the immature virus an attractive target for structure-based drug development one needs to know its chemical structure. Unfortunately, the complexity and size of the viral particle — an incomplete hexagonal shell with a size close to 100 nm — have prevented the experimental determination of the chemical, namely atomic level, structure of the virus. 

CPLC graduate fellow, Boon Chong Goh and CPLC postdoctoral fellow, Juan Perilla, led a collaboration between the Schulten group at CPLC and Beckman Institute and the Craven group at Pennsylvania State University, and provided the first atomic structure of immature retroviral lattice for the Rous Sarcoma Virus. The multi-domain RSV model was derived through a combination of state-of-the-art modeling techniques, including, cryo-EM-guided homology modeling, large-scale molecular dynamics simulations  together with experimental measurements such as X-ray crystallography and biochemical data. Particularly, the model reveals novel features of the packing and dynamics of the immature capsid protein with implications for the maturation process and confirms the stabilizing roles of the so-called upstream and downstream domains of the immature RSV. More information is available on the journal webpage ( and in a highlight video (