Computational protocol: Antivirals for allosteric inhibition of Zika virus using a homology model and experimentally determined structure of envelope protein

Similar protocols

Protocol publication

[…] The amino acid sequence of ZVEP was resolved initially using Zika virus’ 10,794-nucleotide National Center for Biotechnology Information (NCBI) NC_012532.1 [] via Basic Local Alignment Search Tool (BLAST) []. Then using the BLAST-protein module, sequences that matched the ZVEP were retrieved. This search was aided by a profile/function search performed using Interpro [] embedded in Swiss-model [] protein modeling tool. The result was a 500-amino-acid ZVEP segment that contained key domains likely responsible for glycosidic interactions (Fig. a). Then using SWISS-MODEL workspace [], a template search with was performed using BLAST and HHBlits against the SWISS-MODEL Template Library (SMTL). The models with the highest quality based on the features of the target-template alignment were selected for model building.Fig. 1 Based on the target-template alignment, homology models were built via Promod-II []. Conserved coordinates between the target and the template were copied from the template to the model. Insertions and deletions were remodeled using a fragment library. Then, side-chains were rebuilt. Lastly, the geometry of the model was regularized by using force fields. The overall and per-residue model quality was assessed using the QMEAN4 [] and Global Model Quality Estimation (GMQE) scoring functions as shown in Fig. c, d. Each residue is assigned a QMEAN reliability score between zero and one, describing the expected similarity to the native structure and higher numbers indicate a greater reliability of the residues. GMQE combines properties from the target-template alignment, and the score is expressed as above reflecting the expected accuracy of a model built with that alignment and template.Dengue virus envelope protein (WNEP, PDB ID: 3j27) was identified to be the best template to be used for the development of the final ZVEP homology model and a three-dimensional model for the target protein was generated (Fig. b). Model quality assessment tools were used to assess the reliability of the resulting models are given in the inset (Fig. c, d). The predicted ZVEP homology structure (yellow—Fig. b), when overlaid with that of 5IRE for comparison (blue—Fig. b), shows >50% structural identity preserved indicating the model’s utility as a proxy for studying ZVEP behavior. […]

Pipeline specifications

Software tools BLASTN, SWISS-MODEL, HHblits, QMEAN
Applications Protein structure analysis, Amino acid sequence alignment
Organisms Zika virus
Diseases HIV Infections
Chemicals Amino Acids