The solution of crystal structures and in-depth structural analysis play a pivotal role in current efforts for rational antibody-based vaccine design. However, the structures for many important targets, such as viral surface proteins, haven proven extremely difficult to determine using traditional methods such as protein crystallization or NMR. This presents a significant obstacle to structure-based vaccine design efforts, which rely heavily on the availability of high-quality atomic-level structural information. Computational tools that allow modeling and simulation of proteins at different levels of structural detail can provide a rational basis for the molecular design of edited proteins more suitable for crystallization, thus enabling atomic-level characterization of otherwise evasive targets. Moreover, once the structure of a particular target is determined, computational tools can also assist in structural analysis, to help extract its full biological meaning and to guide new experimental efforts. In particular, here we develop and utilize computational tools to assist in protein crystallization and structural analysis.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Zip Code
Xu, Kai; Acharya, Priyamvada; Kong, Rui et al. (2018) Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1. Nat Med 24:857-867
Rutten, Lucy; Lai, Yen-Ting; Blokland, Sven et al. (2018) A Universal Approach to Optimize the Folding and Stability of Prefusion-Closed HIV-1 Envelope Trimers. Cell Rep 23:584-595
Zhou, Tongqing; Zheng, Anqi; Baxa, Ulrich et al. (2018) A Neutralizing Antibody Recognizing Primarily N-Linked Glycan Targets the Silent Face of the HIV Envelope. Immunity 48:500-513.e6
Wang, Lingshu; Shi, Wei; Chappell, James D et al. (2018) Importance of neutralizing monoclonal antibodies targeting multiple antigenic sites on MERS-CoV Spike to avoid neutralization escape. J Virol :
Kisalu, Neville K; Idris, Azza H; Weidle, Connor et al. (2018) A human monoclonal antibody prevents malaria infection by targeting a new site of vulnerability on the parasite. Nat Med 24:408-416
Kwong, Peter D; Mascola, John R (2018) HIV-1 Vaccines Based on Antibody Identification, B Cell Ontogeny, and Epitope Structure. Immunity 48:855-871
Andrews, Sarah F; Joyce, M Gordon; Chambers, Michael J et al. (2017) Preferential induction of cross-group influenza A hemagglutinin stem-specific memory B cells after H7N9 immunization in humans. Sci Immunol 2:
Chuang, Gwo-Yu; Geng, Hui; Pancera, Marie et al. (2017) Structure-Based Design of a Soluble Prefusion-Closed HIV-1 Env Trimer with Reduced CD4 Affinity and Improved Immunogenicity. J Virol 91:
Xu, Ling; Pegu, Amarendra; Rao, Ercole et al. (2017) Trispecific broadly neutralizing HIV antibodies mediate potent SHIV protection in macaques. Science 358:85-90
Curreli, Francesca; Kwon, Young Do; Belov, Dmitry S et al. (2017) Synthesis, Antiviral Potency, in Vitro ADMET, and X-ray Structure of Potent CD4 Mimics as Entry Inhibitors That Target the Phe43 Cavity of HIV-1 gp120. J Med Chem 60:3124-3153

Showing the most recent 10 out of 36 publications