GENETIC MUTATIONS AND THEIR STRUCTURAL AND FUNCTIONAL IMPACT ON ENZYMES: A COMPREHENSIVE REVIEW
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Objective: Genetic mutations play a fundamental role in shaping enzyme structure, dynamics, and catalytic function, thereby influencing biological evolution, disease mechanisms, and biotechnological innovation. Understanding the relationship between genotype and enzymatic phenotype remains a major scientific challenge, particularly in predicting the functional consequences of missense and non-synonymous mutations. Method: This review provides a comprehensive examination of the structural and functional impact of genetic mutations on enzymes, emphasizing advances in computational and biophysical methodologies. Classical molecular dynamics simulations offer atomic-level insights into conformational flexibility and allosteric communication, while quantum mechanics/molecular mechanics (QM/MM) approaches elucidate catalytic mechanisms and electronic transitions during enzymatic reactions. Additionally, emerging machine learning strategies enable large-scale prediction of mutational effects and rational enzyme engineering by exploring complex sequence–structure–function relationships. Results: Variations ranging from single nucleotide substitutions to larger structural alterations may induce subtle or profound changes in protein folding, stability, substrate specificity, and reaction kinetics. The integration of physics-based simulations and data-driven models represents a transformative framework for understanding mutation-induced enzymatic alterations, accelerating enzyme design, improving predictive accuracy, and expanding applications in industrial biocatalysis and therapeutic development. Novelty: Such multidisciplinary approaches accelerate enzyme design, improve predictive accuracy, and expand applications in industrial biocatalysis and therapeutic development. Continued methodological innovation is essential to bridge existing gaps in correlating genetic variation with enzymatic performance.
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