In Silico Predictive Homology Modeling of PKHD-1 Protein: A Comparative Study among Three Different Species

Abstract

Abstract Background: The PKHD-1 (Polycystic Kidney and Hepatic Disease-1) gene encodes a crucial protein vital for renal and hepatic functions. Mutations in PKHD-1 result in Autosomal Recessive Polycystic Kidney Disease (ARPKD), a severe disorder in early infancy. Despite its significance, the structural information on PKHD-1 remains limited, with few low-resolution structures accessible. Homology Modeling was employed to generate structural models of PKHD-1 proteins from three species: Homo sapiens (Human), Mus musculus (Mouse), and Canis lupus familiaris (Dog). Various bioinformatics tools were utilized for analysis and validation. Results: Structural models of PKHD-1 proteins from different species were generated using Homology Modeling and advanced bioinformatics tools, including SWISS-Model, ProtParam, GOR4, PROSA Web, ExPasy QMEANDisCo, and P2Rank. The primary structure, physicochemical properties, and secondary structure of PKHD-1 proteins were analyzed and validated. Binding pockets critical for understanding functional roles and potential therapeutic interventions were predicted using the P2Rank tool. Conclusion: This study provides comprehensive structural insights into PKHD-1 proteins across multiple species. Rigorous validation of homology models through Z-Score analysis and QMEANDisCo Global Score ensures their reliability and accuracy. The identification of binding pockets offers potential targets for therapeutic interventions. Comparative analysis of PKHD-1 protein structures enhances understanding of evolutionary relationships and lays the foundation for future comparative functional studies. This research significantly contributes to structural biology and biomedical research, serving as a valuable resource for researchers investigating PKHD-1 function, disease mechanisms, and drug targeting strategies. The findings pave the way for exploring species-specific functions and adaptations of PKHD-1, fostering advancements in the understanding and treatment of ARPKD and related disorders.