Multiscale Computational Microscopy of HIV-1

HIV-1 的多尺度计算显微镜

• 批准号: 10756808
• 负责人: Rommie E Amaro
• 金额: $ 71.39万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-07 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10756808
• 关键词: 2019-nCoV; AIDS prevention; Acquired Immunodeficiency Syndrome; Address; Antigens; Back; Biology; Cells; Chimeric Proteins; Collaborations; Crowding; Cryo-electron tomography; Cryoelectron Microscopy; Data; Data Set; Disease; Elements; Exhibits; Future Generations; Glycocalyx; Goals; HIV; HIV vaccine; HIV-1; Heparitin Sulfate; Human; Immune system; Infection; Infection prevention; Influenza; Knowledge; Link; Methods; Microscope; Microscopy; Modeling; Molecular Structure; Mucins; Mutate; Outcome; Pattern; Persons; Physiological; Play; Polysaccharides; Post-Translational Protein Processing; Protein Dynamics; RNA; Resolution; Retroviridae; Scientist; Series; Site; Structural Biologist; Structure; Surface; Techniques; Therapeutic; Time; Translating; United States National Institutes of Health; Utah; Vaccines; Viral; Viral Fusion Proteins; Viral Proteins; Virion; Virus; advanced simulation; density; design; env Gene Products; experimental study; flexibility; immunogenic; improved; in vivo; infection rate; insight; interest; model building; molecular dynamics; novel; receptor; simulation; small molecule; structural biology

ABSTRACT The human immunodeficiency virus 1 (HIV-1) is the RNA retrovirus that causes acquired immunodeficiency syndrome (AIDS), a disease that has killed over 40 million people worldwide and infected more than twice that. Continued high infection rates has made understanding of HIV biology and vaccines a high priority. A key molecule involved in both infection and vaccine efforts is the HIV-1 Envelope protein (Env). Experimental structural biology techniques have characterized the basic structure of Env, but they are unable to provide details about the extensive N-linked glycan shield nor inform on the flexibility and dynamics of Env. In this proposal, we envision using all-atom molecular dynamics simulations as a `computational microscope,' to provide insights into the dynamics of Env that are unattainable with current experimental techniques. Together with top flight experimentalists, we will develop and simulate a series of models to explore the dynamics of Env as well as its interactions with co-receptors and the cell glycocalyx, in unprecedented detail. In addition, we will use advanced simulation techniques to optimize immunogen design as well as provide critical information about hitherto unseen druggable sites in Env.

摘要