Version 1
: Received: 30 August 2024 / Approved: 2 September 2024 / Online: 2 September 2024 (13:35:48 CEST)
How to cite:
Sanapalli, V.; Sigalapalli, D. K.; Shaik, A. B.; Bhandare, R. R.; Sanapalli, B. K. R. Computational Elucidation of Human β-defensin-2 as a Dual Inhibitor of MMP-9 and PKC-βII for Diabetic Wound Management. Preprints2024, 2024090112. https://doi.org/10.20944/preprints202409.0112.v1
Sanapalli, V.; Sigalapalli, D. K.; Shaik, A. B.; Bhandare, R. R.; Sanapalli, B. K. R. Computational Elucidation of Human β-defensin-2 as a Dual Inhibitor of MMP-9 and PKC-βII for Diabetic Wound Management. Preprints 2024, 2024090112. https://doi.org/10.20944/preprints202409.0112.v1
Sanapalli, V.; Sigalapalli, D. K.; Shaik, A. B.; Bhandare, R. R.; Sanapalli, B. K. R. Computational Elucidation of Human β-defensin-2 as a Dual Inhibitor of MMP-9 and PKC-βII for Diabetic Wound Management. Preprints2024, 2024090112. https://doi.org/10.20944/preprints202409.0112.v1
APA Style
Sanapalli, V., Sigalapalli, D. K., Shaik, A. B., Bhandare, R. R., & Sanapalli, B. K. R. (2024). Computational Elucidation of Human β-defensin-2 as a Dual Inhibitor of MMP-9 and PKC-βII for Diabetic Wound Management. Preprints. https://doi.org/10.20944/preprints202409.0112.v1
Chicago/Turabian Style
Sanapalli, V., Richie R. Bhandare and Bharat Kumar Reddy Sanapalli. 2024 "Computational Elucidation of Human β-defensin-2 as a Dual Inhibitor of MMP-9 and PKC-βII for Diabetic Wound Management" Preprints. https://doi.org/10.20944/preprints202409.0112.v1
Abstract
Diabetic wound (DW) is the most devastating complication resulting in significant mortality and morbidity in diabetic patients. Although the pathophysiology of DWs is multifaceted, evidence revealed that prolonged inflammation with infections, extracellular matrix (ECM) degradation and unnecessary NETosis impair DW healing. This theoretical problem commands the necessity of developing a novel strategy focused on targeting the 'specific' molecular modalities of DW. The primary culprits, matrix metalloproteinase (MMP)-9 and protein kinase C (PKC)-βII, are responsible for impaired angiogenesis, NETosis, and ECM degradation. Thus, there is reinvigorated interest in identifying selective inhibitors for the effective management of DW. The current study exemplified human β-defensin-2 (HBD-2), a biological macromolecule as a dual-inhibitor of MMP-9 and PKC-βII using protein-protein docking and molecular dynamics simulation studies. Residue-residue interactions and binding affinity were investigated using Z-dock. Chemical bonding behavioral changes, structural dynamics, and functional changes were determined using GROMACS by analyzing RMSD, ROG, RMSF, SASA, FEL, and PCA. Overall, the data analysis revealed that HBD-2 possesses strong binding affinity and stability against MMP-9 and PKC-βII, which can be an ideal therapeutic for the accelerated healing of DW. The study provides valuable insights into the molecular mechanisms underlying hBD-2's potential therapeutic effects, offering new avenues for the development of innovative treatment strategies. The clinical relevance of our findings lies in their potential to inform the development of new approaches for diabetic wound management, addressing a significant healthcare concern.
Keywords
Diabetic wound; Human β-defensin-2; Matrix metalloproteinase-9; Protein kinase C-βII; Protein-protein docking; Molecular dynamics simulation studies.
Subject
Medicine and Pharmacology, Dermatology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
