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Molecular Dynamics Simulations of Certain RGD-Based Peptides from Kistrin Provide Insight into the Higher Activity of REI-RGD34 Protein at Higher Temperature

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Title Molecular Dynamics Simulations of Certain RGD-Based Peptides from Kistrin Provide Insight into the Higher Activity of REI-RGD34 Protein at Higher Temperature
 
Creator UPADHYAY, SK
 
Subject bioactive
GROMACS
integrin receptors
kistrin
REI-RGD34
RGD
simulation
CRYSTAL-STRUCTURE
ANTAGONISTS
GPIIB/IIIA
INTEGRINS
FAMILY
DOMAIN
 
Description To determine the bioactive conformation required to bind with receptor IIb3, the peptide sequence RIPRGDMP from Kistrin was inserted into CDR 1 loop region of REI protein, resulting in REI-RGD34. The activity of REI-RGD34 was observed to increase at higher temperature towards the receptor IIb3. It could be justified in either way: the modified complex forces the restricted peptide to adapt bioactive conformation or it unfolds the peptide in a way that opens its binding surface with high affinity for receptor. Here, we model the conformational preference of RGD sequence in RIPRGDMP at 25 and 42 degrees C using multiple MD simulations. Further, we model the peptide sequence RGD, PRGD and PRGDMP from kistrin to observe the effect of flanking residues on conformational sampling of RGD. The presence of flanking residues around RGD peptide greatly influenced the conformational sampling. A transition from bend to turn conformation was observed for RGD sequence at 42 degrees C. The turn conformation shows pharmacophoric parameters required to recognize the receptor IIb3. Thus, the temperature-dependent activity of RIPRGDMP when inserted into the loop region of REI can be explained by the presence of the turn conformation. This study will help in designing potential antagonist for the receptor IIb3.
 
Publisher WILEY-BLACKWELL
 
Date 2014-12-28T15:03:24Z
2014-12-28T15:03:24Z
2014
 
Type Article
 
Identifier CHEMICAL BIOLOGY & DRUG DESIGN, 83(5)600-609
1747-0277
1747-0285
http://dx.doi.org/10.1111/cbdd.12275
http://dspace.library.iitb.ac.in/jspui/handle/100/16823
 
Language English