Wnt-4 is an important signaling protein of the Wnt family that acts in paracrine manner to a few cell diameters. Wnt-4 takes part in many developmental processes including sex determination, and kidney development and also plays role in brain as well. Wnt-4 has a total of 25 cysteine residues with conserved locations in relation to whole Wnt family. Due to unchallenged importance of Wnts and to study their unusual fold, Wnt-4 was considered for simulation to interpret and extract structural features dynamically. Comparative modeling approach was utilized to model Wnt-4 and minimized to remove any energy restraints. The minimized model was then subjected to molecular dynamics simulation with periodic boundary conditions, to understand its behavior in the presence of water-box. Wnt-4 behavior for 20-nanosecond (ns) simulation was analyzed by calculating the root mean square deviation (RMSD), root mean square fluctuation (RMSF), and b-factor. Prominently, twenty (20) cysteine residues were observed in the edges of loops participating in interactions with frizzled receptors. The higher values of RMSD with comparison to higher values of RMSF and b-factor of residues accompanying 20 cysteine residues lying in regions nearer to N- and C-terminal domains extrapolate that these residues might be involved in cysteine–cysteine disulfide linkages and are more important structurally and functionally as well. Display omitted •Energy minimization•Structure validation•Molecular dynamics simulation•Connection of function and structural variability of the Wnt-4•Importance of thumb-index fold