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Molecular Dynamics Simulations of Certain RGD ‐Based Peptides from Kistrin Provide Insight into the Higher Activity of REI ‐ RGD 34 Protein at Higher Temperature
Author(s) -
Upadhyay Sanjay K.
Publication year - 2014
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12275
Subject(s) - peptide , chemistry , sequence (biology) , stereochemistry , molecular dynamics , receptor , conformational change , biophysics , biochemistry , biology , computational chemistry
To determine the bioactive conformation required to bind with receptor α II b β 3, the peptide sequence RIPRGDMP from Kistrin was inserted into CDR 1 loop region of REI protein, resulting in REI ‐ RGD 34. The activity of REI ‐ RGD 34 was observed to increase at higher temperature towards the receptor α II b β 3. 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 °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 °C. The turn conformation shows pharmacophoric parameters required to recognize the receptor α II b β 3. 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 α II b β 3.