The enzyme Tyrosinase (TYR), responsible for the catalysis of the early stages of
melanogenesis in various organisms, is described in some groups. Among those that
stand out: hyperpigmentation, melasma and skin cancer, in not melanoma forms and
malignant melanoma. In general, dysfunctions are treated with depigmenting agents,
TYR enzyme alerts. However, among them is the kojic acid (KA), marked side effects.
Such phenomena make a TYR a model of biological development of drug prototypes.
In the meantime, I investigated some TYR enzyme inhibitory genes, in particular AK
and analogous plants, as well as a Tropolone and some benzaldehyde derivatives,
structurally related to the natural substrates of TYR (L-Tyrosine and L-Dopa), as the
Molecular Docking, Molecular Dynamics (MD), and the Linear Interaction Energy (LIE)
method, used to calculate the free binding energy of the systems. Specifically
application of Molecular Docking defined the mode of binding of the inhibitors in the
TYR site, being possible to quantify how interactions occur in the systems. As the MD
simulations, they exhibited the effect of the enzyme with different inhibitors and how
they act when complexed with a TYR enzyme, using a copper dummy atom model.
Thus, the results obtained by LIE were concordant with the experimental results,
obtaining an R2 of 0.91 in a linear regression of LIE vs Experimental, and this allowed
to analyze how Tropolona, KA, MOL2 and MOL3 interactions with the important to the
active site of TYR. Thus, the results achieved at work contributed significantly to the
achievement of inhibition of the TYR enzyme, helping to combat the evils caused by a
cycle of melanin production in organisms.
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