Protein-engineered biomaterials represent a powerful approach to increase biofunctional activity like tissue repair and celular proliferation. Among these materials, integrins and the development of their specific interactions with plasma-polymerized pyrrole (PPPy) are promising biomaterial for tissue regeneration. In this paper, we studied the molecular recognition in the active site of three integrins (α5β1, αvβ3 and αIIbβ3) with PPPy using the structure proposed by Kumar et al . PPPy molecule has three sites to incorporate different species, we worked mainly with the functional groups, –NH 2 and –OH groups according to our IR spectroscopic results. We carried out docking studies to find the better conformational couplings and to determine electrostatic (ΔG elec ) and non-electrostatic (ΔG non-elec ) contributions to the binding free energy (ΔG b ) of these complexes we used Adaptive Poisson-Bolztmann program (APBS). Our results indicated that when incorporating -1H-azirine, -NH 2 or –OH group in PPPy structure, interactions with integrins were favorable, as indicated by correspondent ΔG b values. These interactions were mainly triggered by Coulomb interactions, an important term in the electrostatic component. Furthermore, our studies suggest that some residues of integrins α5β1, αvβ3 and αIIbβ3 like aspartates are important for the binding to PPPy structures. Detailed interactions between integrin α5β1 and PPPy structures were revealed by molecular dynamics simulations. We used this particular integrin structure because of its favorable ΔG b as well as its major cellular receptor for the extracellular matrix protein fibronectin. Clustering analysis allowed us to carry out focused docking studies and to determine the time evolution of the ΔG b values. By incorporating -NH 2 into PPPy structure, ΔG b values were very favorable during the course of the dynamics simulations by the establishment of hydrogen bonds with Asn224 and/or Asp227 residues, which are part of the integrin α5β1 pocket. However, for the integrin α5β1-PPPy-1H-azirine complex and the rest of the functional groups, the ΔG b values were less favorable, although PPPy was found at a distance of less than 5 Å from the active site residues. This work is complementary to the previous studies made employing PPPy nanoparticles for a variety of tissue engineering applications, and were done to enlighten the role played by the amino group of the PPPy in its integrin recognition process.

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