Properties of concentrated macromolecular solutions

1.设计并制造了一种能够自动测量溶液和其他大分子的粘度对浓度和剪切速率的依赖性的粘度计/流变仪。 该仪器进行了深入的验证，通过比较的结果得到的解决方案的小粘度（甘油，蔗糖），合成聚合物，和蛋白质，并在文献中发表的结果，在很宽的浓度和粘度范围。 美国政府已经为该设备申请了专利（A。Grupi & A. Minton）。 2.先前公布的测量结果的依赖性的单克隆抗体的二元混合物的粘度在很宽的范围内的组合物和总蛋白质浓度已成功地模拟使用两个半经验方程，扩展的门尼方程和Krieger-Doughterson方程的广义形式。 进一步推广到自缔合和/或异缔合蛋白质的解决方案。 上文第1部分中概述的工具目前正在用于测试所提出的广义关系对其他蛋白质混合物（包括已知相关的蛋白质）的适用性。 3.我们的实验室目前正在开发一种混合理论和数值模型，用于蛋白质溶液的聚合统计作为离子强度和pH值的函数。我们的目标是创建一个粗粒度的描述，一个定性模型，捕获广泛的系统类的基本属性。我们的模拟集中在一个粗粒度的蛋白质间的静电相互作用领域。有许多方法可以做到这一点，所有方法都涉及到对所涉及的场和力的不同级别的离散化和近似。 我们通过数值求解非线性Poisson-Boltzmann方程来计算蛋白质周围的静电场。 我们试图匹配这个字段尽可能接近使用（小）一组离散的“宏电荷”，这与每个离子强度和pH值不同的假设是，这些“玩具”将给出一个粗略的概念的蛋白质溶液的热力学量散装，指向更详细的实验在体外和在硅片上。许多典型的处理大量的粒子只考虑各向同性的贡献。 通过使用各向异性电场对蛋白质间相互作用进行建模，我们希望在不牺牲计算效率的情况下获得更多的真实感。 一旦场被近似，我们将运行一组蒙特-卡罗实验来确定热力学变量（例如平均能量和比热）。将计算径向分布函数等结构参数，并用于计算光和X射线散射等实验性质，以与实验（Hoppe）进行比较。

1. A viscometer/rheometer capable of automatically measuring the dependence of viscosity of solutions and other macromolecules upon both concentration and shear rate was designed and constructed. The instrument was intensively validated by comparison of results obtained on solutions of small viscogens (glycerol, sucrose), synthetic polymers, and proteins, and published results in the literature, over a wide range of concentrations and viscosities. A U.S. government patent on this device has been applied for (A. Grupi & A. Minton). 2. The results of previously published measurements of the dependence of the viscosity of binary mixtures of monoclonal antibodies over a wide range of composition and total protein concentration have been successfully modeled using generalized forms of two semi-empirical equations, the extended Mooney equation and the Krieger-Dougherty equation. A further generalization to solutions of self- and/or hetero-associating proteins was proposed. The instrument outlined in part 1 above is currently being used to test the applicability of the proposed generalized relations to mixtures of other proteins, including proteins that are known to associate. 3. Our lab is currently developing a hybrid theoretical and numerical model for aggregate statistics of protein solutions as a function of ionic strength and pH. The goal is to create a coarse-grained description, a qualitative model that captures the fundamental properties for a wide class of systems. Our simulations concentrate on a coarse-grained field of inter-protein electrostatic interaction. There are numerous ways of doing this, all involving different levels of discretization and approximation to the fields and forces involved. We calculate the electrostatic field around a protein via numerical solution of the non-linear Poisson-Boltzmann equation. We attempt to match this field as closely as possible using a (small) set of discretized "macro-charges", which vary with each ionic strength and pH. The hypothesis is that these "toys" will give a rough idea of the thermodynamic quantities of a protein solution in bulk, pointing the way toward more detailed experiments both in vitro and in silico. Many typical treatments for a large number of particles consider only a isotropic contribution. By modeling the interprotein interactions using anisotropic electric fields we hope to capture more realism without sacrificing computational efficiency. Once the field has been approximated we will run a battery of Monte-Carlo experiments to determine thermodynamic variables (such as the average energy and the specific heat). Structural parameters such as the radial distribution function will be computed and used to calculate experimental properties such as light and X-ray scattering for comparison with experiment (Hoppe).