w18_empower-aids - HIV Envelope at Multiple Scales [Slides]
Being the sole viral protein entity expressed on the surface of the Human Immunodeficiency Virus (HIV) envelope, the Envelope Glycoprotein (Env) remains the only plausible immunological target. Nevertheless, extreme dynamic heterogeneity, structural complexity, and system size make the study of these glycoproteins immensely challenging. We have utilized the Institutional Computing (IC) resources to overcome some of these challenges in computational modeling of the Env glycoproteins. This integrated technique can sufficiently sample a physiologically relevant conformational space accessible to carbohydrates, in a very short time. This method has been validated by quantitatively comparing to experimental cryoEM maps of the HIV Env protein. We have employed graph theory to capture the glycan shield topological network, pinpoint potential interaction pathways, and identify concerted behavior of the glycans. Analyses of various network attributes, such as relative centrality of different glycan positions, identification of communities, and critical subnetwork features, have aided in detailed examination of the glycan shield. Starting from select structures modeled by the pipeline, we are performing large-scale atomistic MD simulations to study the temporal behavior of this system, which will help elucidate biologically relevant antibody behavior. This method can be seamlessly extended to benefit research in Zika, Ebola and other high-density glycosylated systems.
- Research Organization:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- Sponsoring Organization:
- USDOE Laboratory Directed Research and Development (LDRD) Program; USDOE National Nuclear Security Administration (NNSA)
- DOE Contract Number:
- 89233218CNA000001
- OSTI ID:
- 1498017
- Report Number(s):
- LA-UR-19-21873
- Country of Publication:
- United States
- Language:
- English
Similar Records
Vaccination with Glycan-Modified HIV NFL Envelope Trimer-Liposomes Elicits Broadly Neutralizing Antibodies to Multiple Sites of Vulnerability
Structural characterization of a highly-potent V3-glycan broadly neutralizing antibody bound to natively-glycosylated HIV-1 envelope