Abstract
The Ebola virus (EBOV) hijacks normal physiological processes by apoptotic mimicry to be taken up by the cell it infects. The initial adhesion of the virus to the cell is based on the interaction between T cell immunoglobulin and mucin domain protein, TIM, on the cell surface and phosphatidylserine (PS) on the viral outer surface. Therefore, it is important to understand the interaction between EBOV and PS and TIM, with selective blocking of the interaction as a potential therapy. Recent experimental studies have shown that for TIM-dependent EBOV entry, a mucin-like domain with a length of at least 120 amino acids is required, possibly because of the increase of area of the PS-coated surface sampled. We examine this hypothesis by modeling the process of TIM-PS adhesion using a coarse-grained molecular model. We find that the strength of individual bound PS-TIM pairs is essentially independent of TIM length. TIMs with longer mucin-like domains collectively have higher average binding strengths because of an increase in the probability of binding between EBOV and TIM proteins. Similarly, we find that for larger persistence length (less flexible), the average binding force decreases, again because of a reduction in the probability of binding.