Steric effects on multivalent ligand-receptor binding: Exclusion of ligand sites by bound cell surface receptors
Steric effects on multivalent ligand-receptor binding: Exclusion of ligand sites by bound cell surface receptors
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DOI：
10.1016/s0006-3495(99)77456-4
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发表时间：
1999-06-01
影响因子：
3.4
通讯作者：
Perelson, AS
中科院分区：
文献类型：
--
作者：
Hlavacek, WS;Posner, RG;Perelson, AS
位阻效应可以影响细胞表面受体与多价配体的结合。为了解释由受体的大小和配体上结合位点的间距引起的位阻效应，我们通过引入位阻因子扩展了配体-受体相互作用的标准数学模型。该因子给出了受体可接近的未结合配体位点的比例，从而可用于结合，作为配体位点占用的函数。我们推导了各种情况下的位阻因子的表达式，其中受体覆盖在配体表面的致密区域，配体表达在一维或二维中有规则或随机分布的位点。这些表达与配体相关，如线性聚合物、蛋白质和病毒。我们还提出了可用于计算其他情况下位阻因子的数值算法。这些理论结果使我们能够量化位阻对配体-受体动力学和平衡的影响。
Steric effects can influence the binding of a cell surface receptor to a multivalent ligand, To account for steric effects arising from the size of a receptor and from the spacing of binding sites on a ligand, we extend a standard mathematical model for ligand-receptor interactions by introducing a steric hindrance factor. This factor gives the fraction of unbound ligand sites that are accessible to receptors, and thus available for binding, as a function of ligand site occupancy. We derive expressions for the steric hindrance factor for various cases in which the receptor covers a compact region on the ligand surface and the ligand expresses sites that are distributed regularly or randomly in one or two dimensions. These expressions are relevant for ligands such as linear polymers, proteins, and viruses. We also present numerical algorithms that can be used to calculate steric hindrance factors for other cases. These theoretical results allow us to quantify the effects of steric hindrance on ligand-receptor kinetics and equilibria.