DelPhi Suite: New Developments and Review of Functionalities

Li, Chuan; Jia, Zhe; Chakravorty, Arghya; Pahari, Swagata; Peng, Yunhui; Basu, Sankar; Koirala, Mahesh; Panday, Shailesh Kumar; Petukh, Marharyta; Li, Lin; Alexov, Emil

doi:10.1002/jcc.26006

Cited by 54 publications

(49 citation statements)

References 59 publications

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“…Electrostatic potential of surface of VrMPP-b (A) and VrMPP-a (B). Electrostatic potential was calculated using Delphi [90], [91] , with standard parameters. Red, negative; white, neutral; blue, positive.…”

Section: P Smentioning

confidence: 99%

Atomic structures of respiratory complex III₂, complex IV and supercomplex III₂-IV from vascular plants

Maldonado

Guo

Letts

2020

Preprint

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Mitochondrial complex III (CIII2) and complex IV (CIV), which can associate into a higher-order supercomplex (SC III2+IV), play key roles in respiration. However, structures of these plant complexes remain unknown. We present atomic models of CIII2, CIV and SC III2+IV from Vigna radiata determined by single-particle cryoEM. The structures reveal plant-specific differences in the MPP domain of CIII2 and define the subunit composition of CIV. Conformational heterogeneity analysis of CIII2 revealed long-range, coordinated movements across the complex, as well as the motion of CIII2’s iron-sulfur head domain. The CIV structure suggests that, in plants, proton translocation does not occur via the H-channel. The supercomplex interface differs significantly from that in yeast and bacteria in its interacting subunits, angle of approach and limited interactions in the mitochondrial matrix. These structures challenge long-standing assumptions about the plant complexes, generate new mechanistic hypotheses and allow for the generation of more selective agricultural inhibitors.

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Section: P Smentioning

confidence: 99%

Atomic structures of respiratory complex III₂, complex IV and supercomplex III₂-IV from vascular plants

Maldonado

Guo

Letts

2020

Preprint

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“…Further, in each panel, the molecular partner represented as 'cartoon' is colored 'yellow', if it is contributing to the potential (i.e., in case of partner-potentials), and, 'dim gray' otherwise (self-potentials). The electrostatic surface coloring was done in Chimera [108] using Delphi [41] electrostatic focusing files (.cube) with a color scale set to -10 kT/e for 'pure blue' to +10 kT/e for 'pure red'. As can be seen, there is very little match of counter-colors (red and blue's) between corresponding patches on both 'contact surfaces' (ligand and receptor) due their respective self-and partner-potentials -which means weak anti-correlation due to unfavorable electrostatic interactions.…”

Section: Resultsmentioning

confidence: 99%

“…Electrostatic Complementarity (EC) at the protein-protein interfaces was adopted as originally prescribed by McCoy et al, [32] wherein, the surface electrostatic potential was computed for each interfacial protein surface twice, one time each for the contribution of each partner molecule (taken as 'target' and 'neighbor'). The surface electrostatic potentials were computed by numerically solving the Poisson-Boltzmann equation (using Delphi v8.4 [41]) implementing its finite difference method, wherein, the protein dielectric was modeled as a smooth Gaussian function of distance from its center of mass [42]). This returns two troughs of potential values for each intrefacial surface and the negative of the Pearson's correlation is defined as the EC at each interfacial surface (see eq.2).…”

Section: =mentioning

confidence: 99%

Plausible Blockers of Spike RBD in SARS-CoV2 – Molecular Design and Underlying Interaction Dynamics from High-Level Structural Descriptors<b> </b>

Basu¹,

Saha²,

Bhattacharyya³

2020

Preprint

Self Cite

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COVID-19 is characterized by an unprecedented abrupt increase in transmission rate relative to its endemic evolutionary ancestor, SARS-CoV (2003). The complex molecular cascade of events related to the viral pathogenicity is triggered by the Spike protein upon interacting with the ACE2 receptor on human lung cells through its receptor binding domain (RBDSpike). One potential therapeutic strategy to combat COVID-19 could thus be limiting the infection by blocking this key interaction. In this current study, we adapt a protein design approach to predict and propose non-virulent structural mimics of the RBDSpike, potentially serving as its competitive inhibitors in binding to ACE2. RBDSpike is an independently foldable protein domain, resilient to conformational changes upon mutations and therefore an attractive target for strategic re-design. Interestingly, in spite of displaying an optimal shape fit between their interacting surfaces (attributed to a consequently high mutual affinity), the RBDSpike – ACE2 interaction appears to have a quasi-stable character due to a poor electrostatic match at their interface. Structural analyses of homologous complexes reveal that the RBDSpike has an unusually high degree of solvent-exposed hydrophobic residues, attributed to key evolutionary changes, making it inherently ‘reaction-prone’. The designed mimics, aimed to block the viral entry by occupying the available binding sites on ACE2, are tested to have signatures of stable high-affinity binding with ACE2, overriding the native quasi-stable feature. The results show the apt of directly adapting natural examples in the design protocol, wherein, homology-based threading coupled with strategic ‘hydrophobic ↔ polar’ mutations potentially serves as a breakthrough.

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“…DelPhi Suite [75] is available at http://compbio.clemson.edu/sapp/delphi_webserver/ or as a standalone software. This popular platform has been redesigned, utilizing the object-oriented programming technique and other unique features provided by C++ to ensure various levels of multiprocessing and memory distribution.…”

Section: Computational Analysis and Prediction Toolsmentioning

confidence: 99%

Protein electrostatics: From computational and structural analysis to discovery of functional fingerprints and biotechnological design

Vascon

Gasparotto

Giacomello

et al. 2020

Computational and Structural Biotechnology Journal

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Computationally driven engineering of proteins aims to allow them to withstand an extended range of conditions and to mediate modified or novel functions. Therefore, it is crucial to the biotechnological industry, to biomedicine and to afford new challenges in environmental sciences, such as biocatalysis for green chemistry and bioremediation. In order to achieve these goals, it is important to clarify molecular mechanisms underlying proteins stability and modulating their interactions. So far, much attention has been given to hydrophobic and polar packing interactions and stability of the protein core. In contrast, the role of electrostatics and, in particular, of surface interactions has received less attention. However, electrostatics plays a pivotal role along the whole life cycle of a protein, since early folding steps to maturation, and it is involved in the regulation of protein localization and interactions with other cellular or artificial molecules. Short- and long-range electrostatic interactions, together with other forces, provide essential guidance cues in molecular and macromolecular assembly. We report here on methods for computing protein electrostatics and for individual or comparative analysis able to sort proteins by electrostatic similarity. Then, we provide examples of electrostatic analysis and fingerprints in natural protein evolution and in biotechnological design, in fields as diverse as biocatalysis, antibody and nanobody engineering, drug design and delivery, molecular virology, nanotechnology and regenerative medicine.

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DelPhi Suite: New Developments and Review of Functionalities

Cited by 54 publications

References 59 publications

Atomic structures of respiratory complex III₂, complex IV and supercomplex III₂-IV from vascular plants

Atomic structures of respiratory complex III₂, complex IV and supercomplex III₂-IV from vascular plants

Plausible Blockers of Spike RBD in SARS-CoV2 – Molecular Design and Underlying Interaction Dynamics from High-Level Structural Descriptors<b> </b>

Protein electrostatics: From computational and structural analysis to discovery of functional fingerprints and biotechnological design

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DelPhi Suite: New Developments and Review of Functionalities

Cited by 54 publications

References 59 publications

Atomic structures of respiratory complex III2, complex IV and supercomplex III2-IV from vascular plants

Atomic structures of respiratory complex III2, complex IV and supercomplex III2-IV from vascular plants

Plausible Blockers of Spike RBD in SARS-CoV2 – Molecular Design and Underlying Interaction Dynamics from High-Level Structural Descriptors<b> </b>

Protein electrostatics: From computational and structural analysis to discovery of functional fingerprints and biotechnological design

Contact Info

Product

Resources

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Atomic structures of respiratory complex III₂, complex IV and supercomplex III₂-IV from vascular plants

Atomic structures of respiratory complex III₂, complex IV and supercomplex III₂-IV from vascular plants