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

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）：本提案的目标是阐明凝聚生物分子系统中诱导极化的性质，并完成蛋白质和磷脂膜的第一代全原子可极化力场。我们已经通过并开始开发一个潜在的功能，采用经典的德鲁德振荡器，电子极化率。我们已经优化了一个简单的水模型（SWM 4-DP），现在准备进入下一阶段。我们的第一个目标将是阐明诱导极化率在凝聚相相对于气相的性质，通过优化力场的一些基本化合物。这些初步的研究也将有助于澄清在凝聚系统中由泡利不相容原理和电子云重叠引起的诱导电子极化率的根本降低。我们的第二个目标是优化力场的内部部分。我们的第三个目标将是通过对晶体环境中的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，脂膜界面势的本质将通过对脂双层的完全可极化模型和导致钙与钙结合蛋白中EF手协同结合的阳离子-配体相互作用进行MD模拟来阐明。必须强调的是，拟议研究中的三个目标是以迭代的方式联系在一起的。在拟议的研究完成后，一个新的力场蛋白质和脂质，包括明确的治疗电子极化率将提供给科学界。虽然拟议的研究将使用CHARMM程序进行，但用于治疗电子极化率的经典Drude振荡器的简单性将确保开发的力场可以很容易地在其他模拟软件包中实现。