Dynamic cross correlation analysis of Thermus thermophilus alkaline phosphatase and determinants of thermostability

Borges, Bruno; Gallo, Gloria; Coelho, Camila; Negri, Naiane; Maiello, Fernando; Hardy, Leon; Würtele, Martin

doi:10.1016/j.bbagen.2021.129895

Cited by 9 publications

(6 citation statements)

References 58 publications

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“…Because this -TΔS value is similar, the task of ranking the binding can be thus in most cases simplified in first approximation to comparison of the other binding energy values. The somewhat atypical -TΔS value of 47.5 kcal/mol for the GETEQKRIRK peptide is possibly the result of its increased number of large, positively charged residues, which will induce more vibrational and rotational movements, including side-chain rotamer states [49] , [50] . These states are stabilized upon binding, leading to a reduction of conformational entropy.…”

Section: Resultsmentioning

confidence: 99%

A proteomics-MM/PBSA dual approach for the analysis of SARS-CoV-2 main protease substrate peptide specificity

et al. 2022

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Section: Resultsmentioning

confidence: 99%

A proteomics-MM/PBSA dual approach for the analysis of SARS-CoV-2 main protease substrate peptide specificity

et al. 2022

Self Cite

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“…The DCC algorithm is unchanged from that of MD-TASK, with the exception that it is now faster and supports additional atom types. Some of the recent examples from the published literature that used the MD-TASK DCC functionality include [16] , [17] , [18] , [21] .…”

Section: Resultsmentioning

confidence: 99%

“…Both MD-TASK and MODE-TASK have been highly utilized to mine protein dynamics by offering a series of novel approaches that have demonstrated their applicability in a growing number of cases [6] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] . Although both software suites are relatively easy to use, the required technical knowledge and software dependencies may act as a hurdle against more widespread usage of the tools and techniques, due to the diversity of operating systems and the relatively fast-evolving Python libraries.…”

Section: Introductionmentioning

confidence: 99%

MDM-TASK-web: MD-TASK and MODE-TASK web server for analyzing protein dynamics

Amamuddy

Glenister

Tshabalala

et al. 2021

Computational and Structural Biotechnology Journal

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Highlights Web server for MD-TASK and MODE-TASK, with new tools and updates. Eight dynamic residue network centrality metrics for analyzing protein molecular dynamics, extended for static proteins. Comparative essential dynamics for improved comparison of independent molecular dynamic simulations of related proteins. A communication propensity tool for evaluating residue communication efficiency. Normal mode analysis of proteins from static structures and molecular dynamic simulations.

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“…Although mammalian alkaline phosphatases have been known as allosteric enzymes for many years [ 18 ], the dynamics-driven allosteric signaling pathways have yet to be investigated at an atomistic level. Therefore, the elucidation of the conformational dynamics and allosteric signatures of TNSALP caused by ALPL mutations would provide greater insight into the genotype-phenotype relationship in HPP [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Dissecting mutational allosteric effects in alkaline phosphatases associated with different Hypophosphatasia phenotypes: An integrative computational investigation

Xiao

Zhou²,

Song³

et al. 2022

PLoS Comput Biol

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Hypophosphatasia (HPP) is a rare inherited disorder characterized by defective bone mineralization and is highly variable in its clinical phenotype. The disease occurs due to various loss-of-function mutations in ALPL, the gene encoding tissue-nonspecific alkaline phosphatase (TNSALP). In this work, a data-driven and biophysics-based approach is proposed for the large-scale analysis of ALPL mutations-from nonpathogenic to severe HPPs. By using a pipeline of synergistic approaches including sequence-structure analysis, network modeling, elastic network models and atomistic simulations, we characterized allosteric signatures and effects of the ALPL mutations on protein dynamics and function. Statistical analysis of molecular features computed for the ALPL mutations showed a significant difference between the control, mild and severe HPP phenotypes. Molecular dynamics simulations coupled with protein structure network analysis were employed to analyze the effect of single-residue variation on conformational dynamics of TNSALP dimers, and the developed machine learning model suggested that the topological network parameters could serve as a robust indicator of severe mutations. The results indicated that the severity of disease-associated mutations is often linked with mutation-induced modulation of allosteric communications in the protein. This study suggested that ALPL mutations associated with mild and more severe HPPs can exert markedly distinct effects on the protein stability and long-range network communications. By linking the disease phenotypes with dynamic and allosteric molecular signatures, the proposed integrative computational approach enabled to characterize and quantify the allosteric effects of ALPL mutations and role of allostery in the pathogenesis of HPPs.

show abstract

Dynamic cross correlation analysis of Thermus thermophilus alkaline phosphatase and determinants of thermostability

Cited by 9 publications

References 58 publications

A proteomics-MM/PBSA dual approach for the analysis of SARS-CoV-2 main protease substrate peptide specificity

A proteomics-MM/PBSA dual approach for the analysis of SARS-CoV-2 main protease substrate peptide specificity

MDM-TASK-web: MD-TASK and MODE-TASK web server for analyzing protein dynamics

Dissecting mutational allosteric effects in alkaline phosphatases associated with different Hypophosphatasia phenotypes: An integrative computational investigation

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