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Akankshya Satapathy, Mairepaiti Halimulati and Tatiana Guaraca
Introduction
Introduction
Sphingosine kinase 1 (SPHK1) is a key enzyme in the sphingolipid metabolism pathway, responsible for converting sphingosine into sphingosine-1-phosphate (S1P), a bioactive lipid that regulates diverse cellular functions including proliferation, apoptosis, angiogenesis, and immune responses [1]. Dysregulation of SPHK1 expression or activity has been implicated in various cancers, including prostate cancer, where elevated SPHK1 levels have been associated with increased tumor aggressiveness and poor prognosis. Understanding the structural and functional consequences of mutations in the SPHK1 protein may offer new insights into mechanisms of prostate tumor progression and provide potential targets for therapeutic intervention [2].
Advances in bioinformatics and protein modeling have made it possible to analyze sequence variability and predict structural changes induced by mutations [3]. In this study, a combination of multiple sequence alignment (MSA), structural modeling using AlphaFold, and mutation effect prediction tools such as SIFT and PolyPhen were used to investigate prostate cancer-associated SPHK1 mutations. By integrating sequence conservation, structural positioning, and functional domain mapping, we aim to characterize the potential impact of key missense mutations on the conformation and activity of the SPHK1 protein.
Hypothesis 1:
Hypothesis 1:
Distribution and Frequency of SPHK1 Mutations in Prostate Cancer
Distribution and Frequency of SPHK1 Mutations in Prostate Cancer
Mutations in SPHK1 associated with prostate cancer may not be randomly distributed; instead, they may cluster in specific regions of the gene. Using Python, we will analyze the mutation distribution across the SPHK1 gene, quantify their frequency, and determine whether mutations are concentrated in certain hotspots.
Hypothesis 2:
Hypothesis 2:
Conservation of SPHK1 Mutations in Prostate Cancer
Conservation of SPHK1 Mutations in Prostate Cancer
SPHK1 mutations identified in prostate cancer occur at evolutionarily conserved amino acid residues. If these sites are highly conserved across species, it would suggest they are functionally important and that mutations at these positions may contribute to cancer development.
Hypothesis 3:
Hypothesis 3:
Functional Impact of Mutations on SPHK1 Domains
If prostate cancer-associated SPHK1 mutations cluster in conserved regions, they are more likely to disrupt important protein functions.
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