Insights from the Interfaces of Corona Viral Proteins: Homomers Versus Heteromers

2021 ◽  
Vol 14 (3) ◽  
pp. 1613-1631
Author(s):  
Christina Nilofer ◽  
Arumugam Mohanapriya
Keyword(s):  
Hydrogen Bond ◽  
Viral Proteins ◽  
Viral Disease ◽  
Electrostatic Energy ◽  
Interface Area ◽  
Hydrogen Bond Energy ◽  
Biochemical Biomarkers ◽  
Protein Interfaces ◽  
Life Threatening ◽  
Percent Contribution

The outbreak of COVID-19 and its mutant variants has become a life-threatening and fatal viral disease to mankind. Several studies have been carried out to identify an effective receptor against coronavirus using clinically driven samples distinguished as hematological, immunological and biochemical biomarkers. Simultaneously, protein interfaces are being researched to understand the structural and functional mechanism of action. Therefore, we characterized and examined the interfaces of corona viral proteins using a dataset consisting of 366 homomeric and 199 heteromeric protein interfaces. The interfaces were analyzed using six parameters including interface area, interface size, van der Waal, hydrogen bond, electrostatic and total stabilizing energies. We observed the interfaces of corona viral proteins (homomer and heteromer) to be alike. Therefore, we clustered the interfaces based on the percent contribution of vdW towards total stabilizing energy as vdW energy dominant (≥60%) and vdW energy subdominant (<60%). We found 91% of interfaces to have vdW energy in dominance with large interface size [146±29 (homomer) and 122±29 (heteromer)] and interface area [1690±683 (homomer) and 1306±355 (heteromer)]. However, we also observed 9% of interfaces to have vdW energy in sub-dominance with small interface size [60±12 (homomer) and 41±20 (heteromer)] and interface area [472±174 (homomer) and 310±199 (heteromer)]. We noticed the interface area of large interfaces to be four-fold more when compared to small interfaces in homomer and heteromer. It was interesting to observe that the small interfaces of homomers to be rich in electrostatics (r2=0.50) destitute of hydrogen bond energy (r2=0.04). However, the heteromeric interfaces were equally pronounced with hydrogen bond (r2=0.70) and electrostatic (r2=0.61) energies. Hence, our earlier findings stating that the small protein interfaces are rich in electrostatic energy remaintrue with the homomeric interfaces of corona viral proteins whereas not in heteromeric interfaces.

scholarly journals Insights from the interfaces of HIV-1 envelope (ENV) trimer viral protein GP160 (GP120-GP41)

2021 ◽  
Vol 12 (1) ◽  
pp. 513-522
Author(s):  
Christina Nilofer ◽  
Arumugam Mohanapriya
Keyword(s):  
Hydrogen Bonds ◽  
Viral Protein ◽  
Van Der Waals ◽  
Interface Area ◽  
Protein Interfaces ◽  
Gp120 Protein ◽  
Life Threatening ◽  
Total Energies ◽  
Potential Vaccine ◽  
Hiv 1

The Human Immunodeficiency Virus (HIV-1) type 1 viral protein is a life threatening virus causing HIV/AIDS in infected humans. The HIV-1 envelope (ENV) trimer glycoprotein GP160 (GP120-GP41) is gaining attention in recent years as a potential vaccine candidate for HIV-1/AIDS. However, the sequence variation and charge polarity at the interacting sites across clades is a shortcoming faced in the development of an effective HIV-1 vaccine. We analyzed the interfaces in terms of its interface area, interface size, and interface energies (van der Waals, hydrogen bonds, and electrostatics). The interfaces were divided as dominant (≥60%) and subdominant (<60%) based on van der Waals contribution to total energies. 88% of GP120 and 74% of GP41 interfaces are highly pronounced with van der Waals energy having large interfaces with interface size (98±65 (GP120) and 73±65 (GP41)) and interface area (882±1166Å2 (GP120) and 921±1288Å2 (GP41)). Nevertheless, 12% of GP120 and 26% of GP41 interfaces have subdominant van der Waals energies having small interfaces with interface size (58±20 (GP120) and 27±9 (GP41)) and interface area (581±1605Å2 (GP120) and 483±896Å2 (GP41)). It was interesting to observe GP41 small interfaces with subdominant van der Waals are stabilized by electrostatics (r2=0.63) without hydrogen bonds (r2=0). However, GP120 small interfaces were found to have two fold more hydrogen bonds (r2=0.59) than electrostatics (r2=0.20). Therefore, our previous finding stating that small protein-protein interfaces rich in electrostatics holds true in case of GP41 whereas not with GP120 protein interfaces.

Insight into structure, stability and hydrogen bond in complexes of guanine and thymine at the molecular level using computational chemical method

2021 ◽  
Vol 11 (1) ◽  
pp. 127-134
Author(s):  
Nhung Ngo Thi Hong ◽  
Huong Dau Thi Thu ◽  
Trung Nguyen Tien
Keyword(s):  
Hydrogen Bond ◽  
Hydrogen Bonds ◽  
Energy Surface ◽  
Covalent Bond ◽  
Electrostatic Energy ◽  
Substantial Contribution ◽  
Structure Stability ◽  
Dispersion Terms ◽  
Insight Into

Nine stable structures of complexes formed by interaction of guanine with thymine were located on potential energy surface at B3LYP/6-311++G(2d,2p). The complexes are quite stable with interaction energy from -5,8 to -17,7 kcal.mol-1. Strength of complexes are contributed by hydrogen bonds, in which a pivotal role of N−H×××O/N overcoming C−H×××O/N hydrogen bond, up to to 3.5 times, determines stabilization of complexes investigated. It is found that polarity of N/C−H covalent bond over proton affinity of N/O site governs stability of hydrogen bond in the complexes. The obtained results show that the N/C−H×××O/N red-shifting hydrogen bonds occur in all complexes, and a larger magnitude of an elongation of N−H compared C-H bond length accompanied by a decrease of its stretching frequency is detected in the N/C−H×××O/N hydrogen bond upon complexation. The SAPT2+ analysis indicates the substantial contribution of attractive electrostatic energy versus the induction and dispersion terms in stabilizing the complexes.

Relation between hydrogen bond energy and total surface energy of some hydrogen bonded liquids

2010 ◽  
Vol 83 (5-6) ◽  
pp. 197-200
Author(s):  
K. Srinivasa Manja ◽  
B. Krishnan ◽  
T. K. Nambinarayanan ◽  
A. Srinivasa Rao
Keyword(s):  
Hydrogen Bond ◽  
Surface Energy ◽  
Bond Energy ◽  
Total Surface Energy ◽  
Hydrogen Bond Energy ◽  
Hydrogen Bonded

Correlations of NHN hydrogen bond energy with geometry and1H NMR chemical shift difference of NH protons for aniline complexes

2019 ◽  
Vol 150 (11) ◽  
pp. 114305 ◽  
Author(s):  
E. Yu. Tupikina ◽  
M. Sigalov ◽  
I. G. Shenderovich ◽  
V. V. Mulloyarova ◽  
G. S. Denisov ◽  
...  
Keyword(s):  
Hydrogen Bond ◽  
Chemical Shift ◽  
Bond Energy ◽  
Nmr Chemical Shift ◽  
Hydrogen Bond Energy ◽  
Chemical Shift Difference

scholarly journals Identification of Lysine Acetylation Sites on MERS-CoV Replicase pp1ab

2020 ◽  
Vol 19 (8) ◽  
pp. 1303-1309 ◽  
Author(s):  
Lin Zhu ◽  
Sin-Yee Fung ◽  
Guangshan Xie ◽  
Lok-Yin Roy Wong ◽  
Dong-Yan Jin ◽  
...  
Keyword(s):  
Viral Proteins ◽  
Bioinformatic Analysis ◽  
Hek293 Cells ◽  
Lysine Acetylation ◽  
Protein Acetylation ◽  
Conservation Level ◽  
Life Threatening ◽  
Infected Cells ◽  
Orbitrap Analysis ◽  
First Time

MERS is a life-threatening disease and MERS-CoV has the potential to cause the next pandemic. Protein acetylation is known to play a crucial role in host response to viral infection. Acetylation of viral proteins encoded by other RNA viruses have been reported to affect viral replication. It is therefore of interest to see whether MERS-CoV proteins are also acetylated. Viral proteins obtained from infected cells were trypsin-digested into peptides. Acetylated peptides were enriched by immunoprecipitation and subject to nano-LC-Orbitrap analysis. Bioinformatic analysis was performed to assess the conservation level of identified acetylation sites and to predict the upstream regulatory factors. A total of 12 acetylation sites were identified from 7 peptides, which all belong to the replicase polyprotein pp1ab. All identified acetylation sites were found to be highly conserved across MERS-CoV sequences in NCBI database. Upstream factors, including deacetylases of the SIRT1 and HDAC families as well as acetyltransferases of the TIP60 family, were predicted to be responsible for regulating the acetylation events identified. Western blotting confirms that acetylation events indeed occur on pp1ab protein by expressing NSP4 in HEK293 cells. Acetylation events on MERS-CoV viral protein pp1ab were identified for the first time, which indicate that MERS-CoV might use the host acetylation machinery to regulate its enzyme activity and to achieve optimal replication. Upstream factors were predicted, which might facilitate further analysis of the regulatory mechanism of MERS-CoV replication.

Evaluating the Predictive Abilities of Protocols Based on Hydrogen-Bond Propensity, Molecular Complementarity, and Hydrogen-Bond Energy for Cocrystal Screening

2020 ◽  
Vol 20 (11) ◽  
pp. 7320-7327
Author(s):  
Nandini Sarkar ◽  
Nina C. Gonnella ◽  
Mariusz Krawiec ◽  
Dongyue Xin ◽  
Christer B. Aakeröy
Keyword(s):  
Hydrogen Bond ◽  
Bond Energy ◽  
Hydrogen Bond Energy ◽  
Molecular Complementarity ◽  
Cocrystal Screening

scholarly journals Understanding Rad51 function is a prerequisite for progress in cancer research

QRB Discovery ◽  
2020 ◽  
Vol 1 ◽  
Author(s):  
Bengt Nordén ◽  
Masayuki Takahashi
Keyword(s):  
Hydrogen Bond ◽  
Base Stacking ◽  
Hydrogen Bond Energy ◽  
Rad51 Protein ◽  
Sufficient Detail ◽  
Dna Base ◽  
Single Base Mismatch ◽  
Base Mismatch ◽  
Kinetic Effects ◽  
New Mutations

AbstractThe human protein Rad51 is double-edged in cancer contexts: on one hand, preventing tumourigenesis by eliminating potentially carcinogenic DNA damage and, on the other, promoting tumours by introducing new mutations. Understanding mechanistic details of Rad51 in homologous recombination (HR) and repair could facilitate design of novel methods, including CRISPR, for Rad51-targeted cancer treatment. Despite extensive research, however, we do not yet understand the mechanism of HR in sufficient detail, partly due to complexity, a large number of Rad51 protein units being involved in the exchange of long DNA segments. Another reason for lack of understanding could be that current recognition models of DNA interactions focus only on hydrogen bond-directed base pair formation. A more complete model may need to include, for example, the kinetic effects of DNA base stacking and unstacking (‘longitudinal breathing’). These might explain how Rad51 can recognize sequence identity of DNA over several bases long stretches with high accuracy, despite the fact that a single base mismatch could be tolerated if we consider only the hydrogen bond energy. We here propose that certain specific hydrophobic effects, recently discovered destabilizing stacking of nucleobases, may play a central role in this context for the function of Rad51.

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