Structural complementarity of distance constraints obtained from chemical cross‐linking and amino acid coevolution

Abstract

The analysis of amino acid coevolution has emerged as a practical method for protein structural modeling by providing structural contact information from alignments of amino acid sequences. In parallel, chemical cross‐linking/mass spectrometry (XLMS) has gained attention as a universally applicable method for obtaining low‐resolution distance constraints to model the quaternary arrangements of proteins, and more recently even protein tertiary structures. Here, we show that the structural information obtained by XLMS and coevolutionary analysis are effectively complementary: the distance constraints obtained by each method are almost exclusively associated with non‐coincident pairs of residues, and modeling results obtained by the combination of both sets are improved relative to considering the same total number of constraints of a single type. The structural rationale behind the complementarity of the distance constraints is discussed and illustrated for a representative set of proteins with different sizes and folds.

Tightening the Crosslinking Distance Restraints for Better Resolution of Protein Structure and Dynamics

“…On the other hand, failure to account for all Cu-Cu distance restraints may indicate large-scale protein dynamics, which requires the invocation of additional ll Resource conformational state(s). The structure refinement can also be facilitated and corroborated by other types of restraints, either experimental (Tang and Gong, 2020;Wang et al, 2017) or theoretical (Dos Santos et al, 2020).…”

Amentoflavone, New Hope against SARS-CoV-2: An Outlook through its Scientific Records and an in silico Study

“…[58] Using completely automated frameworks and databases, the homology modelling process is optimized and standardized, enabling even those without a specialized computational background to create accurate protein maps and have a fast and clear reference to modeling findings, representation, and evaluation. [59,60] The amino acid sequence of 3CL PRO (Uniprot accession ID: P0DTD1), and TMPRSS-2 (Uniprot accession ID: O15393) was subjected to NCBI BLAST Program for selection of the closest homologous template Homology model of 3CL PRO , and TMPRSS-2 was generated by Swiss model (Figure 2). Optimization of 3CL PRO and TMPRSS-2 was achieved by using the Swiss-PDB Viewer software package (v.4.1.0) before docking, whereas validation of these 3CL PRO , and TMPRSS-2 homology model was acquired through the use of Ramachandran plot performed by PROCHECK [45] and illustrated in Figure 3.…”