Half a century of Ramachandran plots

Carugo, Oliviero; Djinović-Carugo, Kristina

doi:10.1107/s090744491301158x

Cited by 83 publications

(74 citation statements)

References 86 publications

(98 reference statements)

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“…The Ramachandran plot represents one of the most powerful tools for the analysis of protein structures . In the last half a century, it has been a remarkable source of inspiration for the structural biology community since it straightforwardly delineates allowed/forbidden conformations, in terms of φ and ψ dihedral angles, of amino acid residues within proteins.…”

Section: Introductionmentioning

confidence: 99%

“…The Ramachandran plot represents one of the most powerful tools for the analysis of protein structures. [1][2][3] In the last half a century, it has been a remarkable source of inspiration for the structural biology community since it straightforwardly delineates allowed/forbidden conformations, in terms of u and w dihedral angles, of amino acid residues within proteins. This plot has also been extensively used for the analysis of specific protein structural features as function of u and w. In this framework, the study of the mutual dependence of residue geometry and conformation has been particularly intriguing.…”

Section: Introductionmentioning

confidence: 99%

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The determinants of bond angle variability in protein/peptide backbones: A comprehensive statistical/quantum mechanics analysis

2015

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The elucidation of the mutual influence between peptide bond geometry and local conformation has important implications for protein structure refinement, validation, and prediction. To gain insights into the structural determinants and the energetic contributions associated with protein/peptide backbone plasticity, we here report an extensive analysis of the variability of the peptide bond angles by combining statistical analyses of protein structures and quantum mechanics calculations on small model peptide systems. Our analyses demonstrate that all the backbone bond angles strongly depend on the peptide conformation and unveil the existence of regular trends as function of ψ and/or φ. The excellent agreement of the quantum mechanics calculations with the statistical surveys of protein structures validates the computational scheme here employed and demonstrates that the valence geometry of protein/peptide backbone is primarily dictated by local interactions. Notably, for the first time we show that the position of the H(α) hydrogen atom, which is an important parameter in NMR structural studies, is also dependent on the local conformation. Most of the trends observed may be satisfactorily explained by invoking steric repulsive interactions; in some specific cases the valence bond variability is also influenced by hydrogen-bond like interactions. Moreover, we can provide a reliable estimate of the energies involved in the interplay between geometry and conformations.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The determinants of bond angle variability in protein/peptide backbones: A comprehensive statistical/quantum mechanics analysis

2015

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“…50 After screening, the 262th simulation conformer was identified as a high-quality structure ( Figure 1) and was used as the model for the following dynamic analysis. In general, if the percentage of amino acid residues in the allowable region (red region) and the maximum allowable region (blue region) accounted for more than 90% of the total protein, the conformation of the model could be thought to conform to the rules of stereochemistry.…”

Section: System Preparationmentioning

confidence: 99%

Exploring the effect of E76K mutation on SHP2 cause gain‐of‐function activity by a molecular dynamics study

Wei

Sun

et al. 2018

J of Cellular Biochemistry

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Juvenile myelomonocytic leukemia (JMML), an invasive myeloproliferative neoplasm, is a childhood disease with very high clinical lethality. Somatic mutation E76K in SHP2 is the most commonly identified mutation found in up to 35% of patients with JMML. To investigate the effect of gain-of-function mutation-E76K on SHP2 activity, molecular dynamic simulations on the wild-type SHP2 (SHP2-WT) system and the mutated E76K (SHP2-E76K) system were performed. The evaluation of stability of these two systems indicated that the simulated trajectories were stable after simulation for 3 nanoseconds. The root mean square fluctuation and the per-residue root mean square deviation illustrated that there were two regions (residues Tyr 81-Glu 83 and Glu 258-Leu 261) in the wild-type system and the mutated system, which had large differences. The principal component analysis, dynamic cross correlation maps analysis, as well as secondary structure analysis suggested that the mutated E76K impacted the movement of these two regions in SHP2 protein. Furthermore, residue interaction network analysis, hydrogen bond occupancy, and binding free energies analysis were used to explain how the two regions were specifically affected by the mutant. The results indicated that the primary variances between SHP2-WT and SHP2-E76K were the different interactions between Glu/Lys 76 and Arg 265, Tyr 80 and Leu 77, Leu 77 and Tyr 81, Thr 73 and Glu 258, Ala 75 and Cys 259, Phe 71 and Tyr 81, Ala 75 and Glu 258, and Tyr 73 and Glu/Lys 76. Consequently, these findings here might provide insights into the increased activity in SHP2-E76K.

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“…46 After screening, the 21th simulation conformer of the SHP2-WT ( Figure 1A) and the 100th simulation conformer of the SHP2-N308D ( Figure 1B) were selected from the 501 simulation conformers in the 10-nanosecond MD simulation as the initial structure to run the MD simulations, respectively. Ramachandran Plot denoted the dihedral angle of α carbon, where ϕ (Phi) denoted the rotation angle of the C-N bond and ψ (Psi) represented the rotation angle of the C-C bond in a peptide unit.…”

Section: Shp2-wt and Shp2-n308d Structuresmentioning

confidence: 99%

Exploring the effect of N308D mutation on protein tyrosine phosphatase‐2 cause gain‐of‐function activity by a molecular dynamics study

Sun

Chen

Wang

et al. 2018

J of Cellular Biochemistry

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One of the most common protein tyrosine phosphatase‐2 (SHP2) mutations in Noonan syndrome is the N308D mutation, and it increases the activity of the protein. However, the molecular basis of the activation of N308D mutation on SHP2 conformations is poorly understood. Here, molecular dynamic simulations were performed on SHP2 and SHP2‐N308D to explore the effect of N308D mutation on SHP2 cause gain of function activity, respectively. The principal component analysis, dynamic cross‐correlation map, secondary structure analysis, residue interaction networks, and solvent accessible surface area analysis suggested that the N308D mutation distorted the residues interactions network between the allosteric site (residue Gly244‐Gly246) and C‐SH2 domain, including the hydrogen bond formation and the binding energy. Meanwhile, the activity of catalytic site (residue Gly503‐Val505) located in the Q‐loop in mutant increased due to this region's high fluctuations. Therefore, the substrate had more chances to access to the catalytic activity site of the precision time protocol domain of SHP2‐N308D, which was easy to be exposed. In addition, we had speculated that the Lys244 located in the allosteric site was the key residue which lead to the protein conformation changes. Consequently, overall calculations presented in this study ultimately provide a useful understanding of the increased activity of SHP2 caused by the N308D mutation.

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Half a century of Ramachandran plots

Cited by 83 publications

References 86 publications

The determinants of bond angle variability in protein/peptide backbones: A comprehensive statistical/quantum mechanics analysis

The determinants of bond angle variability in protein/peptide backbones: A comprehensive statistical/quantum mechanics analysis

Exploring the effect of E76K mutation on SHP2 cause gain‐of‐function activity by a molecular dynamics study

Exploring the effect of N308D mutation on protein tyrosine phosphatase‐2 cause gain‐of‐function activity by a molecular dynamics study

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