Trister Andrew D, Hammer Daniel A
Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Biophys J. 2008 Jul;95(1):40-53. doi: 10.1529/biophysj.107.118430. Epub 2008 Mar 13.
We simulated the docking of human immunodeficiency virus (HIV) with a cell membrane using Brownian adhesive dynamics. The main advance in the current version of Brownian adhesive dynamics is that we use a simple bead-spring model to coarsely approximate the role of gp120 trimerization on HIV docking. We used our simulations to elucidate the effect of env spike density on the rate and probability of HIV binding, as well as the probability that each individual gp120 trimer is fully engaged. We found that for typical CD4 surface densities, viruses expressing as few as 8 env spikes will dock with binding rate constants comparable to viruses expressing 72 spikes. We investigated the role of cellular receptor diffusion on the degree of binding achieved by the virus on both short timescales (where binding has reached steady state but before substantial receptor accumulation in the viral-cell contact zone has occurred) and long timescales (where the system has reached steady state). On short timescales, viruses with 10-23 env trimers most efficiently form fully engaged trimers. On long timescales, all gp120 in the contact area will become bound to CD4. We found that it takes seconds for engaged trimers to cluster CD4 molecules in the contact zone, which partially explains the deleay in viral entry.
我们使用布朗粘附动力学模拟了人类免疫缺陷病毒（HIV）与细胞膜的对接。当前版本的布朗粘附动力学的主要进展在于，我们使用简单的珠簧模型来粗略近似gp120三聚化在HIV对接中的作用。我们利用模拟来阐明包膜刺突密度对HIV结合速率和概率的影响，以及每个单独的gp120三聚体完全参与结合的概率。我们发现，对于典型的CD4表面密度，表达仅8个包膜刺突的病毒与表达72个刺突的病毒对接时，其结合速率常数相当。我们研究了细胞受体扩散在短时间尺度（结合已达到稳态但在病毒-细胞接触区尚未发生大量受体积累之前）和长时间尺度（系统已达到稳态）上病毒实现的结合程度中的作用。在短时间尺度上，具有10 - 23个包膜三聚体的病毒最有效地形成完全参与结合的三聚体。在长时间尺度上，接触区域中的所有gp120都会与CD4结合。我们发现，已参与结合的三聚体在接触区聚集CD4分子需要数秒时间，这部分解释了病毒进入的延迟。
