Sequence–function correlation of the transmembrane domains in NS4B of HCV using a computational approach

Huang, Ta-Chou; Fischer, Wolfgang B.

doi:10.3934/biophy.2021013

Cited by 1 publication

(1 citation statement)

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“…Bitopic viral channel forming proteins (VCPs) are used as a test case since they are forming homo-oligomers. In the first stage the helical stretch of the TMD needs to be identified using secondary structure prediction programs (see, e.g., [ 13 , 14 ]). Next, a biologically relevant assumption is that the extramembrane domains and the TMDs act independently upon folding; it is assumed that the TMDs will assemble almost independently of the extramembrane domains.…”

Section: Introductionmentioning

confidence: 99%

Predicting the Assembly of the Transmembrane Domains of Viral Channel Forming Proteins and Peptide Drug Screening Using a Docking Approach

Huang¹,

Fischer²

2022

Biomolecules

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A de novo assembly algorithm is provided to propose the assembly of bitopic transmembrane domains (TMDs) of membrane proteins. The algorithm is probed using, in particular, viral channel forming proteins (VCPs) such as M2 of influenza A virus, E protein of severe acute respiratory syndrome corona virus (SARS-CoV), 6K of Chikungunya virus (CHIKV), SH of human respiratory syncytial virus (hRSV), and Vpu of human immunodeficiency virus type 2 (HIV-2). The generation of the structures is based on screening a 7-dimensional space. Assembly of the TMDs can be achieved either by simultaneously docking the individual TMDs or via a sequential docking. Scoring based on estimated binding energies (EBEs) of the oligomeric structures is obtained by the tilt to decipher the handedness of the bundles. The bundles match especially well for all-atom models of M2 referring to an experimentally reported tetrameric bundle. Docking of helical poly-peptides to experimental structures of M2 and E protein identifies improving EBEs for positively charged (K,R,H) and aromatic amino acids (F,Y,W). Data are improved when using polypeptides for which the coordinates of the amino acids are adapted to the Cα coordinates of the respective experimentally derived structures of the TMDs of the target proteins.

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Section: Introductionmentioning

confidence: 99%