DOI: 10.4103/bbrj.bbrj_262_25 ISSN: 2588-9834
In silico Characterization of Histidine Decarboxylase and SLIT and NTRK-like Family Member 1 Proteins in Tourette Syndrome: A Structural and Molecular Docking Approach
Lulwah Zeyad Aljumaiah
Background:
Histidine decarboxylase (
HDC
) and SLIT and NTRK-like family member 1 (
SLITRK1
) are genes implicated in Tourette syndrome (TS) through roles in histaminergic neurotransmission, synaptic signaling, and neurodevelopment. This study aimed to characterize the structural and functional properties of their encoded proteins and assess their potential pharmacological relevance using an integrative
in silico
approach.
Methods:
Human
HDC
and
SLITRK1
sequences and variant data were obtained from public databases and analyzed using computational tools for physicochemical profiling, secondary-structure prediction, protein interaction analysis, structural modeling, binding-site prediction, molecular docking, and adsorption, distribution, metabolism, excretion, and toxicity (ADMET) assessment. Three-dimensional protein models were generated using AlphaFoldDB-assisted template modeling with refinement and validation. A panel of clinically relevant neuroactive compounds was screened for predicted interactions with both proteins.
Results:
HDC
and
SLITRK1
displayed distinct physicochemical and structural features consistent with their biological functions. Variant analysis identified multiple missense and clinically reported variants in both genes, supporting their functional significance. Network analyses linked
HDC
mainly to histamine synthesis and metabolic pathways, whereas
SLITRK1
was more strongly associated with synaptic organization and neuronal signaling. Structural validation supported the suitability of the predicted models for exploratory analyses. Docking studies identified several compounds with favorable predicted binding affinities for both targets, while ADMET profiling revealed differences in pharmacokinetic and toxicity properties among the screened compounds.
Conclusion:
HDC
and
SLITRK1
are promising candidate proteins in TS. This integrative computational framework may aid prioritization of variants and compounds for future investigation, although experimental validation remains necessary.