Induced Mutation Proves a Potential Target for TB Therapy: A Molecular Dynamics Study on LprG.
In: Cell biochemistry and biophysics, Jg. 76 (2018-09-01), Heft 3, S. 345-356
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Zugriff:
Molecular dynamics (MD) simulations of wild-type and V91W mutant Mycobacterium tuberculosis-LprG (Mtb-LprG) were performed with the goal to provide a comprehensive understanding of the Mtb-LprG as a potential antimycobacterial target. A long-range MD simulations and post-MD analyzes led us to various results that plainly explained the impact of V91W mutation on Mtb-LprG. Herein, the results revealed that the wild-type is less stable compared to V91W mutant. This was further supported by root mean square fluctuation, where the V91W mutant showed a higher degree of flexibility compared to the wild-type. Dynamic cross-correlation analysis revealed that induced mutation leads to higher residual flexibility in the mutant structure as compared to the wild-type structure thus resulting in the existence of negatively correlated motions. The difference in principal component analysis scatter plot across the first two normal modes suggests a greater mobility of the V91W mutant conformation compared to the wild-type. Thermodynamic calculations revealed that the van der Waals (E vdw ) forces contribute the most towards binding free energy in a case of the V91W mutant as compared to the wild-type LprG complex. In addition, the residue interaction networks revealed more of E vdw interaction existence among residues in case of the V91W mutant. This study supports the Mtb-LprG as a potential antimycobacterial target and also serves as a cornerstone to identifying new potential targets that have no inhibitors.
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Induced Mutation Proves a Potential Target for TB Therapy: A Molecular Dynamics Study on LprG.
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Autor/in / Beteiligte Person: | Machaba, KE ; Mhlongo, NN ; Soliman, MES |
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Zeitschrift: | Cell biochemistry and biophysics, Jg. 76 (2018-09-01), Heft 3, S. 345-356 |
Veröffentlichung: | Totowa, NJ : Humana Press, c1996-, 2018 |
Medientyp: | academicJournal |
ISSN: | 1559-0283 (electronic) |
DOI: | 10.1007/s12013-018-0852-7 |
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