scholarly journals Designing BH3-Mimetic Peptide Inhibitors for the Viral Bcl-2 Homologues A179L and BHRF1: Importance of Long-Range Electrostatic Interactions

ACS Omega ◽  
2021 ◽  
Author(s):  
Chinthakunta Narendra Reddy ◽  
Ramasubbu Sankararamakrishnan
Keyword(s):  
Long Range ◽  
Electrostatic Interactions ◽  
Peptide Inhibitors ◽  
Mimetic Peptide ◽  
Bh3 Mimetic

scholarly journals A Computational Pipeline to Design BH3-Mimetic Peptide Inhibitors that Can Bind Specifically to Mcl-1 Or Bcl-XL: Role of Non-Hotspot Residues

2021 ◽  
Vol 120 (3) ◽  
pp. 177a-178a
Author(s):  
Narendra Reddy C ◽  
Nishat Manzar ◽  
Bushra Ateeq ◽  
Ramasubbu Sankararamakrishnan
Keyword(s):  
Peptide Inhibitors ◽  
Computational Pipeline ◽  
Mimetic Peptide ◽  
Bh3 Mimetic

scholarly journals Computational Design of BH3-Mimetic Peptide Inhibitors That Can Bind Specifically to Mcl-1 or Bcl-XL: Role of Non-Hot Spot Residues

Biochemistry ◽  
2020 ◽  
Vol 59 (45) ◽  
pp. 4379-4394
Author(s):  
C. Narendra Reddy ◽  
Nishat Manzar ◽  
Bushra Ateeq ◽  
Ramasubbu Sankararamakrishnan
Keyword(s):  
Hot Spot ◽  
Computational Design ◽  
Peptide Inhibitors ◽  
Mimetic Peptide ◽  
Bh3 Mimetic

scholarly journals Designing BH3-mimetic Peptide Inhibitors for the Viral Bcl-2 Homologs A179L and BHRF1: Importance of long-range electrostatic interactions

2021 ◽  
Author(s):  
C. Narendra Reddy ◽  
Ramasubbu Sankararamakrishnan
Keyword(s):  
Long Range ◽  
Electrostatic Interactions ◽  
African Swine Fever Virus ◽  
Sequence Similarity ◽  
African Swine Fever ◽  
Barr Virus ◽  
Long Range Interactions ◽  
Infected Cells ◽  
Epstein Barr ◽  
Bh3 Mimetic

Viruses have evolved strategies to prevent apoptosis of infected cells at early stages of infection. The viral proteins (vBcl-2s) from specific viral genes adopt a helical fold that is structurally similar to that of mammalian anti-apoptotic Bcl-2 proteins and exhibit little sequence similarity. Hence vBcl-2 homologs are attractive targets to prevent viral infection. However, very few studies have focused on developing inhibitors for vBcl-2 homologs. In this study, we have considered two vBcl-2 homologs, A179L from African swine fever virus and BHRF1 from Epstein-Barr virus. We generated two sets of 8000 randomized BH3-like sequences from eight wild-type pro-apoptotic BH3 peptides. During this process, the four conserved hydrophobic residues and an Asp residue were retained at their respective positions and all other positions were substituted randomly without any bias. We constructed 8000 structures each for A179L and BHRF1 in complex with BH3-like sequences. Histograms of interaction energies calculated between the peptide and the protein resulted in negatively skewed distributions. The BH3-like peptides with high helical propensities selected from the negative tail of respective interaction energy distributions exhibited more favorable interactions with A179L and BHRF1 and they are rich in basic residues. Molecular dynamics studies and electrostatic potential maps further revealed that both acidic and basic residues favorably interact with A179L while only basic residues have the most favorable interactions with BHRF1. As in mammalian homologs, the role of long range interactions and non-hotspot residues have to be taken into account while designing specific BH3-mimetic inhibitors for vBcl-2 homologs.

scholarly journals Polarizable embedding for simulating redox potentials of biomolecules

2019 ◽  
Vol 21 (22) ◽  
pp. 11642-11650 ◽  
Author(s):  
Ruslan N. Tazhigulov ◽  
Pradeep Kumar Gurunathan ◽  
Yongbin Kim ◽  
Lyudmila V. Slipchenko ◽  
Ksenia B. Bravaya
Keyword(s):  
Long Range ◽  
Electrostatic Interactions ◽  
Theoretical Description ◽  
Biological Macromolecules ◽  
Classical Approach ◽  
Redox Potentials ◽  
Computational Protocol ◽  
Polarizable Embedding

We present a computational protocol exploiting polarizable embedding hybrid quantum-classical approach and resulting in accurate estimates of redox potentials of biological macromolecules. A special attention is paid to fundamental aspects of the theoretical description such as the effects of environment polarization and of the long-range electrostatic interactions on the computed energetic parameters.

scholarly journals Distinguishing magnetic and electrostatic interactions by a Kelvin probe force microscopy–magnetic force microscopy combination

2011 ◽  
Vol 2 ◽  
pp. 552-560 ◽  
Author(s):  
Miriam Jaafar ◽  
Oscar Iglesias-Freire ◽  
Luis Serrano-Ramón ◽  
Manuel Ricardo Ibarra ◽  
Jose Maria de Teresa ◽  
...  
Keyword(s):  
Long Range ◽  
Electrostatic Interaction ◽  
Electrostatic Interactions ◽  
Magnetic Force Microscopy ◽  
Magnetic Force ◽  
Superparamagnetic Nanoparticles ◽  
Kelvin Probe Force Microscopy ◽  
Magnetic Interactions ◽  
Kelvin Probe ◽  
Force Microscopy

The most outstanding feature of scanning force microscopy (SFM) is its capability to detect various different short and long range interactions. In particular, magnetic force microscopy (MFM) is used to characterize the domain configuration in ferromagnetic materials such as thin films grown by physical techniques or ferromagnetic nanostructures. It is a usual procedure to separate the topography and the magnetic signal by scanning at a lift distance of 25–50 nm such that the long range tip–sample interactions dominate. Nowadays, MFM is becoming a valuable technique to detect weak magnetic fields arising from low dimensional complex systems such as organic nanomagnets, superparamagnetic nanoparticles, carbon-based materials, etc. In all these cases, the magnetic nanocomponents and the substrate supporting them present quite different electronic behavior, i.e., they exhibit large surface potential differences causing heterogeneous electrostatic interaction between the tip and the sample that could be interpreted as a magnetic interaction. To distinguish clearly the origin of the tip–sample forces we propose to use a combination of Kelvin probe force microscopy (KPFM) and MFM. The KPFM technique allows us to compensate in real time the electrostatic forces between the tip and the sample by minimizing the electrostatic contribution to the frequency shift signal. This is a great challenge in samples with low magnetic moment. In this work we studied an array of Co nanostructures that exhibit high electrostatic interaction with the MFM tip. Thanks to the use of the KPFM/MFM system we were able to separate the electric and magnetic interactions between the tip and the sample.

scholarly journals Exploiting directional long range secondary forces for regulating electrostatics-dominated noncovalent interactions

2017 ◽  
Vol 8 (2) ◽  
pp. 1378-1390 ◽  
Author(s):  
Mrityunjay K. Tiwari ◽  
Kumar Vanka
Keyword(s):  
Long Range ◽  
Electrostatic Interactions ◽  
Noncovalent Interactions ◽  
Supramolecular Complexes ◽  
The Stability

It has been well established that long range secondary electrostatic interactions (SEIs) have a significant effect on the stability of supramolecular complexes.

A refined polarizable water model for the coarse-grained MARTINI force field with long-range electrostatic interactions

2017 ◽  
Vol 146 (5) ◽  
pp. 054501 ◽  
Author(s):  
Julian Michalowsky ◽  
Lars V. Schäfer ◽  
Christian Holm ◽  
Jens Smiatek
Keyword(s):  
Force Field ◽  
Long Range ◽  
Electrostatic Interactions ◽  
Coarse Grained ◽  
Water Model ◽  
Martini Force Field

scholarly journals End-to-end communication in a linear supermolecule with a BOPHY centre and N,N-dimethylanilino-based terminals

2018 ◽  
Vol 42 (7) ◽  
pp. 4835-4842 ◽  
Author(s):  
Owen J. Woodford ◽  
Patrycja Stachelek ◽  
Raymond Ziessel ◽  
Nawaf Algoazy ◽  
Julian G. Knight ◽  
...  
Keyword(s):  
Long Range ◽  
Electrostatic Interactions ◽  
End To End

Long-range electrostatic interactions are sufficient to cause sequential ionization of the terminal groups in a BOPHY-based supermolecule.

Lipid Bilayers Driven to a Wrong Lane in Molecular Dynamics Simulations by Subtle Changes in Long-Range Electrostatic Interactions

2004 ◽  
Vol 108 (14) ◽  
pp. 4485-4494 ◽  
Author(s):  
Michael Patra ◽  
Mikko Karttunen ◽  
Marja T. Hyvönen ◽  
Emma Falck ◽  
Ilpo Vattulainen
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Lipid Bilayers ◽  
Long Range ◽  
Electrostatic Interactions ◽  
Dynamics Simulations
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