Sequence or structure: using bioinformatics and homology modeling to understand functional relationships in cAMP/cGMP binding domains

Abstract

The relationship between sequence, structure, and function is examined by comparing nineteen cyclic nucleotide monophosphate binding domains of known structure from six different functional families. Comparisons are made by structure and sequence alignment and through the generation of 3610 homology models. This analysis suggests there are only weak relationships between functional families, sequence, and/or structure. However, we have identified that for cyclic nucleotide monophosphate binding domains privileged template structures occur for homology modeling. The existence of privileged template structures, capable of creating accurate modeling for a broad family of proteins, may lead to improved homology modeling protocols.

Phylogenetic Diversity and Physiological Roles of Plant Monovalent Cation/H+ Antiporters

“…The main difference between SOS1A and SOS1B is likely to be in the presence of the cyclic nucleotide-binding domain (PF00027), located in the middle of the C-terminus tail ( Figure 1B ). Such cyclic nucleotide-binding domains are known to bind to the wide range of protein targets, in order to regulate multiple cellular processes ( Shabb and Corbin, 1992 ; LaFranzo et al., 2010 ; Rehmann et al., 2017 ; VanSchouwen et al., 2017 ). SOS1A and SOS1B are both localized to the plasma membrane ( Shi et al., 2000 ; An et al., 2007 ) ( Figure 2 ).…”

Effect of Macrotyloma uniflorum on antiobesity in rats fed with a high fat diet

“…The structure of rat pancreatic lipase – RPL (PDB code – 1BU8) and Human Pancreatic lipase – HPL (PDB code – 2PPL) were retrieved from the protein data bank (www.rcsb.org) and adipose triglyceride lipase (ATGL) was predicted by homology modelling MODELLER (Natalie et al, 2010) using ATGL sequence retrieved from NCBI. The refined protein and its possible conformation sites were obtained using a procheck analysis with Ramachandran plot (Laskowsky et al, 1993).…”

Computational Approaches for the Discovery of Human Proteasome Inhibitors: An Overview

“…In the case of a lack of crystallographic structure, partial or complete, homology modeling is the perfect tool to obtain a structure model [73,78,79,80]. Homology modeling’s main goal is to make a prediction of the tridimensional structure of a protein based on the fact that proteins with a homologue amino acid sequence share similar structures (templates) [78,81].…”

“…The choice for creating models must be supported between sequence-related target structures and functionally-related target structures. This fact is mandatory to understand how sequence, function, and structure are interrelated [80]. Validation methodologies can be divided into two different procedures: (1) Stereochemical analyses of the model, focusing on symmetry, geometry, chirality, torsion angles, ligation angles and their distance; (2) Analyses of the correspondence between the sequence and the template (fitness) and attribution of a score to each residue correctly positioned [78].…”