Polarizable Force Field for Proteins and Lipids

蛋白质和脂质的极化力场

• 批准号: 6852507
• 负责人: BENOIT ROUX
• 金额: $ 27.69万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6852507
• 关键词: computer program /software; computer simulation; lipid bilayer membrane; mathematical model; membrane activity; membrane structure; molecular dynamics; molecular polarity; phospholipids; physical state; proteins; water; computer program /software; computer simulation; lipid bilayer membrane; mathematical model; membrane activity; membrane structure; molecular dynamics; molecular polarity; phospholipids; physical state; proteins; water

DESCRIPTION (provided by applicant): The goal of this proposal is to elucidate the nature of induced polarization in condensed biomolecular systems and to complete a first generation all-atom polarizable force field for proteins and phospholipid membranes. We have adopted and started to develop a potential function that incorporates electronic polarizability using classical Drude oscillators. We have optimized a simple water model (SWM4-DP) and are now ready to move to the next phase. Our first aim will be to elucidate the nature of induced polarizability in condensed phases relative to the gas phase by optimizing the force field for a number of basic compounds. These initial studies will also help clarify the fundamental reduction of induced electronic polarizability in condensed systems caused by Pauli's exclusion principle and the overlap of electronic clouds. Our second aim will be to optimize the internal portion of the force field. Our third aim will be to assess the accuracy of the force field by performing molecular dynamics simulations of a test suite of proteins in the crystal environment. In addition, the nature of the interfacial potential of lipid membranes will be elucidated by performing a MD simulation of a fully polarizable model of a lipid bilayer and of the cation-ligand interactions giving rise to cooperative binding of calcium to the EF-hands in calbindin. It is important to emphasize that the three aims in the proposed study are linked in an iterative fashion. Upon completion of the proposed study a novel force field for proteins and lipids that includes explicit treatment of electronic polarizability will be available to the scientific community. While the proposed studies will be performed using the program CHARMM, the simplicity of the classical Drude oscillator used to treat electronic polarizability will insure that the developed force field may be readily implemented in other simulation packages.

描述（由申请人提供）：该提案的目的是阐明凝结的生物分子系统中诱导的极化的性质，并完成用于蛋白质和磷脂膜的第一代全原子极化力场。我们已经采用并开始开发一种潜在的功能，该功能使用经典的Drude振荡器结合了电子极化性。我们已经优化了一个简单的水模型（SWM4-DP），现在准备移至下一阶段。我们的第一个目的是通过优化多种基本化合物的力场来阐明与气相相对于气相中诱导的极化性的性质。这些最初的研究还将有助于阐明由Pauli的排除原理和电子云的重叠引起的凝结系统中诱导的电子极化性的基本降低。我们的第二个目标是优化力场的内部部分。我们的第三个目标是通过在晶体环境中对蛋白质测试套件进行分子动力学模拟来评估力场的准确性。此外，通过对脂质双层的完全极化模型以及阳离子 - 配体相互作用的完全极化模型进行MD模拟，将阐明脂质膜的界面潜力的性质，从而导致钙与Calbindin中的EF手的合作结合。重要的是要强调，拟议的研究中的三个目标是以迭代方式联系起来的。拟议的研究完成后，科学界将获得蛋白质和脂质的新型蛋白质和脂质的力场，包括对电子极化的明确处理。虽然提出的研究将使用程序CHARMM进行，但用于治疗电子极化性的经典Drude振荡器的简单性将确保可以在其他仿真软件包中轻松实现开发的力场。