Polarizable Force Field for Proteins and Lipids

蛋白质和脂质的极化力场

• 批准号: 7289767
• 负责人: BENOIT ROUX
• 金额: $ 25.36万
• 依托单位: UNIVERSITY OF CHICAGO
• 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 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7289767
• 关键词: Address; Adopted; Alcohols; Amides; Amino Acids; Benzene; Binding; Biological; Calcium Binding; Cations; Charge; Classification; Communities; Dipeptides; EF Hand Motifs; Electronics; Environment; Exclusion; Free Energy; Frequencies; Gases; Generations; Glycerol; Goals; Head; Hydration status; Hydrocarbons; Inorganic Sulfates; Lecithin; Ligands; Link; Lipid Bilayers; Lipids; Mechanics; Membrane; Membrane Lipids; Modeling; Molecular; Nature; Numbers; Object Attachment; Phase; Phospholipids; Property; Proteins; Relative (related person); Reproduction; Research Personnel; Source; System; Tail; Testing; Torsion; Unspecified or Sulfate Ion Sulfates; Water; calbindin; density; enthalpy; interfacial; molecular dynamics; novel; programs; quantum; simulation

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发极化的本质，并完成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使用经典德鲁德振荡器结合电子极化性的潜在函数。我们已经优化了一个简单的水模型 (SWM4-DP)，现在准备进入下一阶段。我们的首要目标是通过优化许多基本化合物的力场来阐明凝聚相相对于气相的诱导极化率的性质。这些初步研究还将有助于阐明由泡利不相容原理和电子云重叠引起的凝聚系统中感应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导致钙与钙结合蛋白中的 EF 手协同结合的阳离子-配体相互作用进行 MD 模拟，将阐明脂质膜界面电位的性质。需要强调的是，拟议研究中的三个目标以迭代的方式联系在一起。拟议的研究完成后，科学界将可以使用一种新型的蛋白质和脂质力场，其中包括对电子极化性的明确处理。虽然所提出的研究将使用程序 CHARMM 进行，但用于处理电子极化性的经典德鲁德振荡器的简单性将确保所开发的力场可以在其他模拟包中轻松实现。