Protein docking
and molecular dynamics simulation of predicted IcaA and IcaD protein structure from
Staphylococcus epidermidis involved in PNAG biosynthesis and trafficking
Ramachandira Prabu, Mohanty Amaresh Kumar, Balaji Gupta V.L.N.T., Yadav Rajesh Mudi
and Veeramani T.
Res. J. Biotech.; Vol. 21(2); 235-245;
doi: https://doi.org/10.25303/212rjbt2350245; (2026)
Abstract
IcaA is poly-beta-1,6-N-acetyl-D-glucosamine (PNAG) synthase, an enzyme producing
activated homopolymer chain of N-acetylglucosamine from Staphylococcus epidermidis.
IcaA is an integral membrane-associated N-Acetylglucosamine transferase that requires
accessory IcaD protein for maximal expression and synthesis. We identified icaA
gene sequence carries reputed G-quadruplexes region and characterized 164 bp upstream
promoter sequence of IcaADBC operon. We characterized transcription factor binding
sequence derived from promoter region as PurR, DegU transcription factor and E-Box
invariant sequence. We identified IcaD gene sequence carries E-Box sequence overlap
with IcaB gene of the operon which may act as transcription start site (TSS) for
IcaB gene expression. Due to lack of crystal structure in PDB database, protein
threading methodology was used for construct IcaA and IcaD three-dimensional structure.
Our findings reveal that IcaA C-terminal helices region between Phe295-Arg394 connected
by loops, may act as lid domain of the protein. Asp134, Ile224, Glu226, Asp227,
Arg266, Trp267 are active site amino acids and binding free energy was calculated
as ΔG score −5.13 KJ/mol using Autodock 4.2.6. Molecular dynamics simulation (MDS)
was performed to evaluate stability of IcaA protein, IcaA-UDP-GluNAc binding complex
and IcaD protein throughout trajectories captured within time scale 100 ns simulation
period using GROMACS 4.5. Different binding energies were calculated for IcaA-UDP-GluNAc
complex using GROMACS tools MM-PBSA.
