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VOL. 10, ISSUE 3 (2025)
Transition state analogues in enzyme inhibition: A quantum chemical analysis of organic Vanadates targeting phosphatases.
Authors
Rajanala Srinivas, Dr. Vikas Dubey
Abstract
Transition state analogues (TSAs) play a pivotal role in modern drug
discovery by mimicking the high-energy states of enzyme-catalyzed reactions,
thereby enabling potent and specific inhibition of target enzymes. Among these,
organic vanadates have emerged as promising candidates due to their structural
and electronic similarity to the phosphoryl transfer transition states,
particularly in phosphatases—enzymes that regulate key signal transduction
pathways. This study explores the quantum chemical basis of enzyme inhibition
by organic vanadates, targeting phosphatases implicated in metabolic and
proliferative disorders such as diabetes and cancer. Employing density functional
theory (DFT) and ab initio molecular orbital methods, the electronic structure,
reactivity descriptors, and transition state stabilization of various vanadate
complexes were analyzed. The investigation delves into frontier molecular
orbital interactions, electrostatic potential surfaces, and charge transfer
characteristics to elucidate the mechanistic pathways by which vanadates mimic
the pentavalent phosphate transition states. Computational docking and
interaction energy calculations further corroborate the strong binding affinity
of vanadates to active site residues, demonstrating their potential as
effective transition state inhibitors. Comparative analysis with non-vanadate
analogues highlights the superior stabilization and specificity offered by
vanadium-based inhibitors. Moreover, the study underscores the pharmacophoric
potential of these analogues for developing novel therapeutics against
phosphatase-mediated diseases. The integrative quantum chemical analysis not
only provides mechanistic insights into enzyme inhibition but also offers a
rational framework for the design of next-generation TSA-based inhibitors. This
work contributes to the fundamental understanding of enzyme transition states
and paves the way for exploiting inorganic elements like vanadium in organic
frameworks to achieve targeted biochemical modulation with therapeutic
relevance.
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Pages:13-20
How to cite this article:
Rajanala Srinivas, Dr. Vikas Dubey "Transition state analogues in enzyme inhibition: A quantum chemical analysis of organic Vanadates targeting phosphatases.". International Journal of Advanced Scientific Research, Vol 10, Issue 3, 2025, Pages 13-20
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