To assess the reliability of the protein structural models, various structure verification methods including statistical scoring potential (37, 38), secondary structure compatibility (39) and stereochemical quality check (40) were used.
The resulting model has the correct stereochemistry as gauged from the Ramachandran plot and good three-dimensional (3D) structure compatibility as assessed by the Profiles-3D score.
The hypothesis makes sense only within the context of the entire analysis and considerations presented in this paper which include genomic context, domain composition and secondary structure compatibility evidence.
We use D α (P i, P0) and D Φ, Ψ (P i, P0) to serve as distance metrics to conserve the backbone structures, and D β (P i, P0) to serve as a distance metric to conserve the side-chain structure compatibilities; we also use D H (P i, P0) to serve as a distance metric to conserve the hydrogen bonds.
Finally, sequence-structure compatibility was evaluated by VERIFY-3 D [ 61].
In recent years, new, so-called structurally constrained (SC) models of protein-coding sequence evolution have been proposed, which use statistical potentials to assess sequence-structure compatibility.
Given the quantitative definition of a mutant residual score and its interpretation, the results suggest that PR and RT mutants having increasingly detrimental effects on protein sequence-structure compatibility are also those that are more likely to be associated with a greater degree of drug resistance.
For each PR or RT mutational pattern, this approach allows us to quantify both an overall change in protein sequence-structure compatibility relative to wild-type (residual score) as well as ensuing environmental perturbations (EC scores) at all constituent amino acid positions in the target protein structure, the latter of which define attributes for a feature vector representation of the mutant.
The structural models were analyzed by different structure validation programs including PROCHECK [ 59] for the evaluation of the Ramachandran plot quality, WHATCHECK [ 60] for the calculation of packing quality Z-score, and VERIFY-3 D [ 61] for the evaluation of sequence-structure compatibility (Table 1).
The exact citation, as appeared in the manuscript, is: "The structural models were analyzed by different structure validation programs including PROCHECK [ 59] for the evaluation of the Ramachandran plot quality, WHATCHECK [ 60] for the calculation of packing quality Z-score, and VERIFY-3 D [ 61] for the evaluation of sequence-structure compatibility (Table 1 ).
The compounds have structural compatibility (crystalline structures and crystallites sizes) and good homogeneity.
