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Updated: Aug 29, 2026

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
Published on: July 14, 2015
Improvement of comparative modeling by the application of conserved motifs amongst distantly related proteins as
Saikat Chakrabarti1, Jaisurya John, Ramanathan Sowdhamini
1National Centre for Biological Sciences (TIFR), UAS-GKVK campus, Bellary Road, 560065 Bangalore, India.
Abstract:
Protein comparative modeling has useful applications in large-scale structural initiatives and in rational design of drug targets in medicinal chemistry. The reliability of a homology model is dependent on the sequence identity between the query and the structural homologue used as a template for modeling. Here, we present a method for the utilization and conservation of important structural features of template structures by providing additional spatial restraints in comparative modeling programs like MODELLER. We show that root mean square deviation at C(alpha) positions between the model and the corresponding experimental structure and the quality of the models can be significantly improved for distantly related systems by utilizing additional spatial restraints of the template structures. We demonstrate the influence of such approaches to homology modeling during distant relationships in understanding functional properties of protein such as ligand binding using cytochrome P450 as an example.
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