Fig 1.
Numbers show the steps where tips are applicable.
Table 1.
The protonation states of polar and charged amino acids.
Table 2.
Common biomolecular FFs.
Fig 2.
Case study: Homology modeling of the MAM1 domain in ALK receptor.
(A) Alignment of MAM1 target sequence with potential templates. (B) Homology model built using SwissModel server using the 2v5y.1.A template 3D structure. QMEAN local estimates are shown in colored ribbon (worst in orange to best in blue). (C) Sequence–structure alignment of target template, showing secondary structures calculated via DSSP method and the quality QMEAN local scores in colored bars. (D) Ramachandran outliers for general, glycine, and proline residues. Representative Pro15 and Pro31 residues are shown. The Ramachandran plot shows the values of dihedral angles Φ and Ψ while green contours highlight the optimal expected values. (E) Ab initio prediction via the PEP-FOLD3 server for the region 35 to 52 (ASQMDLLDGPGAERSKEM) showing two α-helices with a GPGA linker. Since this region is relatively large and loop modeling often predicts loop secondary structures, we recommend using an ab initio approach as an additional source for homology modeling (as a template) for more accurate prediction. (F) Local QMEAN estimates before and after manual refinement. The major drops in quality before the refinements were corrected with selective optimization. The lowest QMEAN achieved was −2.44. At this stage, three remaining drops in regions 17 to 19, 37 to 40, and 106 to 112 were not correctable by optimization. ALK, anaplastic lymphoma kinase; DSSP, Dictionary of Secondary Structure of Proteins; QMEAN, Qualitative Model Energy Analysis.