Insights on protein thermal stability: a graph representation of molecular interactions

Miotto, Mattia; Olimpieri, Pier Paolo; Rienzo, Lorenzo Di; Ambrosetti, Francesco; Corsi, Pietro; Lepore, Rosalba; Tartaglia, Gian Gaetano; Milanetti, Edoardo

doi:10.1093/bioinformatics/bty1011

Cited by 84 publications

(59 citation statements)

References 64 publications

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“…Miotto et al presented that, molecular interactions in thermal stress-modified protein revealed that the pattern of modification was closely related to the native-fold, energy-related parameters and to the interaction-networks in its structure. This can characterize differentially thermostable proteins 52 . In our current study we have shown a similar pattern of molecular adaptation in different stress-driven (acid, alkali and thermally stable) proteins.…”

Section: Discussionmentioning

confidence: 99%

Protein stability governed by its structural plasticity is inferred by physicochemical factors and salt bridges

Panja

Maiti

Bandyopadhyay

2020

Sci Rep

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Several organisms, specifically microorganisms survive in a wide range of harsh environments including extreme temperature, pH, and salt concentration. We analyzed systematically a large number of protein sequences with their structures to understand their stability and to discriminate extremophilic proteins from their non-extremophilic orthologs. our results highlighted that the strategy for the packing of the protein core was influenced by the environmental stresses through substitutive structural events through better ionic interaction. Statistical analysis showed that a significant difference in number and composition of amino acid exist among them. The negative correlation of pairwise sequence alignments and structural alignments indicated that most of the extremophile and non-extremophile proteins didn't contain any association for maintaining their functional stability. A significant numbers of salt bridges were noticed on the surface of the extremostable proteins. The Ramachandran plot data represented more occurrences of amino acids being present in helix and sheet regions of extremostable proteins. We also found that a significant number of small nonpolar amino acids and moderate number of charged amino acids like Arginine and Aspartic acid represented more nonplanar omega angles in their peptide bond. thus, extreme conditions may predispose amino acid composition including geometric variability for molecular adaptation of extremostable proteins against atmospheric variations and associated changes under natural selection pressure. the variation of amino acid composition and structural diversifications in proteins play a major role in evolutionary adaptation to mitigate climate change. Modifications in protein structures from organisms that have evolved under extreme environmental conditions differ in how they maintain optimum activity. For example, in the case of halophiles, their optimal growth is associated with their optimal metabolic functions. Heat tolerant organisms are classified as thermophiles, which have optimum growth temperature (OGT) in the range of 45 °C-80 °C and hyper thermophiles with OGT of above 80 °C. Psychrophiles are the organisms which grow on cold condition, that have OGT below 10 °C. Alkalophiles are found in an alkaline p H of more than 9. Alkalophiles and haloalkaliphiles are isolated from extremely alkaline-saline environments, alkaline soil and film such as the Western soda lakes of the United States and Rift valley lakes from East Africa, these are also available from natural environments 1,2. Most of the acidophilic microorganisms survive in low pH by modifying their intracellular protein along with their genome. Evolutionarily conserved protein structures and their sequences showed similarities in their functions but often they differ in their sequence pattern 3. Crystallographic and NMR structures sometimes differ from each other due to their specific experimental condition and retrieval oucome 4-7. The report revealed that proteins with >40% sequence identity may also ...

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Section: Discussionmentioning

confidence: 99%

Protein stability governed by its structural plasticity is inferred by physicochemical factors and salt bridges

Panja

Maiti

Bandyopadhyay

2020

Sci Rep

View full text Add to dashboard Cite

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“…Complemented with known analysis tools, these techniques have been fruitful in characterizing the dynamic rather than just the static causes of thermostability. MD analysis has been complemented by more global analyses of trajectories, including normal-mode analysis (NMA) [11], principal component analysis (PCA) [12] and residue interaction network (RIN) analysis [13,14].…”

Section: Introductionmentioning

confidence: 99%

Crystal structure of Thermus thermophilus methylenetetrahydrofolate dehydrogenase and determinants of thermostability

et al. 2020

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The elucidation of mechanisms behind the thermostability of proteins is extremely important both from the theoretical and applied perspective. Here we report the crystal structure of methylenetetrahydrofolate dehydrogenase (MTHFD) from Thermus thermophilus HB8, a thermophilic model organism. Molecular dynamics trajectory analysis of this protein at different temperatures (303 K, 333 K and 363 K) was compared with homologous proteins from the less temperature resistant organism Thermoplasma acidophilum and the mesophilic organism Acinetobacter baumannii using several data reduction techniques like principal component analysis (PCA), residue interaction network (RIN) analysis and rotamer analysis. These methods enabled the determination of important residues for the thermostability of this enzyme. The description of rotamer distributions by Gini coefficients and Kullback-Leibler (KL) divergence both revealed significant correlations with temperature. The emerging view seems to indicate that a static salt bridge/charged residue network plays a fundamental role in the temperature resistance of Thermus thermophilus MTHFD by enhancing both electrostatic interactions and entropic energy dispersion. Furthermore, this analysis uncovered a relationship between residue mutations and evolutionary pressure acting on thermophilic organisms and thus could be of use for the design of future thermostable enzymes.

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“…Additionally, βcoefficient indicates that aromatic amino acids (Trp+Tyr) contributed more to predicting optimal temperature than polar amino acids ( Table 6). Of note, the low prediction value of this model (53%) is because thermostability cannot be solely predicted from the primary sequences of protein 132 .…”

Section: Multiple Regression Analysismentioning

confidence: 94%

In silico Approach to Elucidate Factors Associated with GH1 β-Glucosidase Thermostability

Ahmed¹,

Sumreen²,

Bibi³

et al. 2019

J Pure Appl Microbiol

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Insights on protein thermal stability: a graph representation of molecular interactions

Cited by 84 publications

References 64 publications

Protein stability governed by its structural plasticity is inferred by physicochemical factors and salt bridges

Protein stability governed by its structural plasticity is inferred by physicochemical factors and salt bridges

Crystal structure of Thermus thermophilus methylenetetrahydrofolate dehydrogenase and determinants of thermostability

In silico Approach to Elucidate Factors Associated with GH1 β-Glucosidase Thermostability

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