MOLECULAR DYNAMICS SIMULATIONS OF BUFORIN II TRANSLOCATION

蟾蜍素 II 易位的分子动力学模拟

• 批准号: 8171887
• 负责人: Donald E. Elmore
• 金额: $ 0.11万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171887
• 关键词: Antibiotics; Bacteria; Cell membrane; Cells; Code; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Drug resistance; Funding; Grant; Institution; Membrane; Membrane Lipids; Molecular; Mutation; Nucleic Acid Binding; Peptides; Publishing; Research; Research Personnel; Resources; Source; Structure-Activity Relationship; System; Techniques; United States National Institutes of Health; antimicrobial; antimicrobial peptide; computing resources; design; experience; improved; insight; killings; magainin; molecular dynamics; novel; simulation

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Antimicrobial peptides represent a potential alternative to conventional antibiotics, particularly against bacteria that have developed drug resistance. One intriguing peptide is buforin II (BF2), which is thought to kill bacteria by crossing the cell membrane and binding nucleic acids inside the cell. Ongoing research in our lab is investigating the BF2 membrane translocation mechanism on the molecular level using a variety of experimental techniques along with molecular dynamics (MD) simulations. Previously, we have primarily focused on simulations of a single BF2 peptide interacting with an explicitly represented lipid membrane, and these simulations provided useful insights into BF2lipid interactions. However, single peptide simulations do not allow us to consider potential cooperativity between peptides in translocation, such as the hypothesized formation of toroidal pores. Thus, are currently considering simulations of multiple BF2 peptides interacting with explicit lipid membranes, similar to recently published simulations of magainin and Tat peptides. We are requesting a developmental allocation to explore the use of TeraGrid for these larger systems that require more extensive computational resources. These simulations will utilize the GROMACS MD code that we employed for previous BF2 simulations. We plan to use our experience from this initial allocation to develop a more extensive TeraGrid proposal considering several BF2 mutations that we are also characterizing experimentally. Together, this computational and experimental data will help elucidate the structure-function relationships of BF2 translocation. An improved understanding of BF2 function will promote the design and application of novel antimicrobial and cell-penetrating peptides.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 抗菌肽代表了传统抗生素的潜在替代品，特别是针对已产生耐药性的细菌。一种有趣的肽是buforin II（BF 2），它被认为通过穿过细胞膜并结合细胞内的核酸来杀死细菌。我们实验室正在进行的研究是在分子水平上使用各种实验技术沿着分子动力学（MD）模拟来研究BF 2膜易位机制。以前，我们主要集中在模拟一个单一的BF 2肽与明确表示的脂质膜相互作用，这些模拟提供了有用的见解BF 2脂质相互作用。然而，单肽模拟不允许我们考虑潜在的协同肽之间的易位，如假设的环形孔的形成。因此，目前正在考虑模拟多种BF 2肽与明确的脂质膜相互作用，类似于最近发表的模拟爪蟾抗菌肽和达特肽。我们正在申请开发拨款，以探索TeraGrid在这些需要更广泛计算资源的大型系统中的应用。这些模拟将利用我们以前用于BF 2模拟的GROMACS MD代码。我们计划利用我们的经验，从这个初始分配，以制定一个更广泛的TeraGrid的建议，考虑到几个BF 2突变，我们也正在实验表征。总之，这些计算和实验数据将有助于阐明BF 2易位的结构-功能关系。对BF 2功能的进一步了解将促进新型抗菌肽和细胞穿透肽的设计和应用。