Theoretical Insights into L-Asparaginases: Guiding the Engineering of Novel Enzymes for Leukemia Therapy

This project focuses on the study of different types and origins of L-asparaginase to enhance their therapeutic potential in leukemia treatment.

L-Asparaginases (ASNases) are enzymes that hydrolyze L-asparagine (Asn) into L-aspartic acid (Asp) and ammonia, playing a key role in leukemia therapy by depriving leukemic cells of Asn, leading to apoptosis.

Our research on L-asparaginases focuses on studying different types and origins of L-asparaginase to enhance their therapeutic potential in leukemia treatment. By combining molecular dynamics simulations, multiscale quantum mechanics/molecular mechanics (QM/MM) approaches and free energy calculations we aim to explore the dynamics, reaction mechanism, substrate specificity and physiologically active oligomeric states of ASNases. This work aims to guide the design of novel enzyme variants with improved activity and reduced immunogenicity, ultimately providing more effective and selective asparaginase-based therapies.