Heparin and heparan sulfate are important
glycosaminoglycans that can regulate the activities of many vital
proteins, especially the fibroblast growth factor (FGF) family. Because
FGF7 (KGF) has an important role in tissue repair and maintaining the
integrity of the mucosal barrier, recombinant human keratinocyte growth
factor (rhKGF, palifermin) has been approved for the treatment of wound
healing and oral cavity. Due to heparin plays an important role in the
KGF signaling pathway, a more detailed study of the drug–drug
interactions (DDIs) between rhKGF and heparin at the atomic level and
investigating their synergistic effect on each other in terms of
biology, especially in silico, is necessary for a better
understanding of DDIs. In this study, DDIs between rhKGF and
low-molecular weight heparin types (LMWH) were investigated. In this
regard, scrutiny of the influence of the synergistic heparin types on
the structure and biostability of rhKGF is accomplished using
computational methods such as molecular docking and molecular dynamic
simulations (MDs). Subsequently, the motion behavior of rhKGF in
interaction with LMWHs was evaluated based on eigenvectors by using
principal component analysis (PCA). Also, the binding free energies of
rhKGF-LMWH complexes were calculated by the molecular
mechanics/Poisson–Boltzmann surface area (MM-BPSA) method. The result
showed that rhKGF-idraparinux (−6.9 kcal/mol) and rhKGF-heparin
(−6.0 kcal/mol) complexes had significant binding affinity as well as
they had a more stable binding to rhKGF than to other LMWH during 100 ns
simulation. However, in order to confirm the curative effect of these
drugs, clinical trials must be done.