Department of Chemical and Biological Engineering, Missouri University of Science and Technology, 400 West 11th Street, Rolla, Missouri 65409-1230, USA.
J Chem Phys. 2010 Aug 28;133(8):084904. doi: 10.1063/1.3473930.
The transport of a charged adsorbate biomolecule in a porous polymeric adsorbent medium and its adsorption onto the covalently immobilized ligands have been modeled and investigated using molecular dynamics modeling and simulations as the third part of a novel fundamental methodology developed for studying ion-exchange chromatography based bioseparations. To overcome computational challenges, a novel simulation approach is devised where appropriate atomistic and coarse grain models are employed simultaneously and the transport of the adsorbate is characterized through a number of locations representative of the progress of the transport process. The adsorbate biomolecule for the system studied in this work changes shape, orientation, and lateral position in order to proceed toward the site where adsorption occurs and exhibits decreased mass transport coefficients as it approaches closer to the immobilized ligand. Furthermore, because the ligands are surrounded by counterions carrying the same type of charge as the adsorbate biomolecule, it takes the biomolecule repeated attempts to approach toward a ligand in order to displace the counterions in the proximity of the ligand and to finally become adsorbed. The formed adsorbate-ligand complex interacts with the counterions and polymeric molecules and is found to evolve slowly and continuously from one-site (monovalent) interaction to multisite (multivalent) interactions. Such a transition of the nature of adsorption reduces the overall adsorption capacity of the ligands in the adsorbent medium and results in a type of surface exclusion effect. Also, the adsorption of the biomolecule also presents certain volume exclusion effects by not only directly reducing the pore volume and the availability of the ligands in the adjacent regions, but also causing the polymeric molecules to change to more compact structures that could further shield certain ligands from being accessible to subsequent adsorbate molecules. These findings have significant practical implications to the design and construction of polymeric porous adsorbent media for effective bioseparations and to the synthesis and operation of processes employed in the separation of biomolecules. The modeling and analysis methods presented in this work could also be suitable for the study of biocatalysis where an enzyme is immobilized on the surface of the pores of a porous medium.
已使用分子动力学建模和模拟对带电荷吸附生物分子在多孔聚合物吸附剂介质中的传输及其与共价固定配体的吸附进行建模和研究，这是为研究基于离子交换色谱的生物分离而开发的新型基础方法的第三部分。为了克服计算方面的挑战，设计了一种新的模拟方法，其中同时使用适当的原子和粗粒模型，并且通过代表传输过程进展的多个位置来描述吸附物的传输。在本工作中研究的系统中，吸附生物分子改变形状、方向和横向位置，以便向发生吸附的位置移动，并随着其接近固定配体，其质量传输系数降低。此外，由于配体被携带与吸附生物分子相同类型电荷的反离子包围，因此生物分子需要反复尝试接近配体，以便置换配体附近的反离子，最终被吸附。形成的吸附物-配体复合物与反离子和聚合物分子相互作用，并且被发现从单一位点（单价）相互作用缓慢且连续地演变为多位置（多价）相互作用。这种吸附性质的转变降低了吸附剂介质中配体的整体吸附能力，并导致表面排除效应。此外，生物分子的吸附还通过不仅直接减少相邻区域中的孔体积和配体的可用性，而且还导致聚合物分子转变为更紧凑的结构，从而进一步阻止某些配体被后续吸附分子接近，从而产生一定的体积排除效应。这些发现对有效生物分离用聚合物多孔吸附剂介质的设计和构建以及用于分离生物分子的过程的合成和操作具有重要的实际意义。本文提出的建模和分析方法也可适用于固定在多孔介质的孔表面上的酶的生物催化研究。
