| Autor: |
Vermeulen, Jan-G, Burt, Felicity, van Heerden, Esta, du Preez-lategaan, Leon, Meiring, Muriel |
| Předmět: |
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| Zdroj: |
Journal of Molecular Modeling; Apr2020, Vol. 26 Issue 4, p1-8, 8p |
| Abstrakt: |
The interaction of a single-chain variable fragment (scFv) directed against human tissue factor (TF) was predicted using an in silico approach with the aim to establish a most likely mechanism of inhibition. The structure of the TF inhibiting scFv (TFI-scFv) was predicted using homology modeling, and complementarity-determining regions (CDRs) were identified. The CDR was utilized to direct molecular docking between the homology model of TFI-scFv and the crystal structure of the extracellular domains of human tissue factor. The rigid-body docking model was refined by means of molecular dynamic (MD) simulations, and the most prevalent cluster was identified. MD simulations predicted improved interaction between TFI-scFv and TF and propose the formation of stable complex for duration of the 600-ns simulation. Analysis of the refined docking model suggests that the interactions between TFI-scFv would interfere with the allosterical activation of coagulation factor VII (FVII) by TF. This interaction would prevent the formation of the active TF:VIIa complex and in so doing inhibit the initiation phase of blood coagulation as observers during in vitro testing. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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