The Molecular Basis of pH-Modulated HIV gp120 Binding Revealed

Morton, Scott P.; Phillips, Julie Baker; Phillips, Joshua

doi:10.1177/1176934319831308

Cited by 4 publications

(6 citation statements)

References 32 publications

(58 reference statements)

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“…Past investigations predict stronger binding affinity between HIV gp120 and human CD4 proteins at lower physiological pH compared to higher physiological pH. Evidence of this was demonstrated by the pipeline EFP and BE data from those protein and complexes [5,6,11,13]. However, the EFP and BE data for s1-ACE2 interactions predict no notable differences in binding efficacy across the physiologically relevant pH range.…”

Section: Resultsmentioning

confidence: 93%

“…We have previously performed extensive research using electrostatic analysis of HIV gp120 envelope glycoprotein interactions with human CD4 and broadly neutralizing antibody proteins [5,6,[11][12][13]15]. Electrostatics are a novel way to evaluate protein interactions at the structural level with a focus on how environmental conditions, like pH, effect binding efficacy.…”

Section: Introductionmentioning

confidence: 99%

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Computational Electrostatics Predict Variations in SARS-CoV-2 Spike and Human ACE2 Interactions

Morton

Phillips

2021

2021 IEEE International Conference on Bioinformatics and Biomedicine (BIBM)

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SARS-CoV-2 is a novel virus that is presumed to have emerged from bats to crossover into humans in late 2019. As the global pandemic ensues, scientist are working to evaluate the virus and develop a vaccine to counteract the deadly disease that has impacted lives across the entire globe. We perform computational electrostatic simulations on multiple variants of SARS-CoV-2 spike protein s1 in complex with human angiotensin-converting enzyme 2 (ACE2) variants to examine differences in electrostatic interactions across the various complexes. Calculations are performed across the physiological pH range to also examine the impact of pH on these interactions. Two of six spike protein s1 variations having greater electric forces at pH levels consistent with nasal secretions and significant variations in force across all five variants of ACE2. Five out of six spike protein s1 variations have relatively consistent forces at pH levels of the lung, and one spike protein s1 variant that has low potential across a wide range of pH. These predictions indicate that variants of SARS-CoV-2 spike proteins and human ACE2 in certain combinations could potentially play a role in increased binding efficacy of SARS-CoV-2 in vivo.

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Section: Resultsmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Computational Electrostatics Predict Variations in SARS-CoV-2 Spike and Human ACE2 Interactions

Morton

Phillips

2021

2021 IEEE International Conference on Bioinformatics and Biomedicine (BIBM)

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“…The virus is often transmitted during sexual intercourse where an acidic mucosa pool exists. Therefore, gp160, which naturally maintains its function in acidic conditions, was purified in a buffer with low pH as suggested from the parsed literature ( 33 ). On the other end, we found protein NaChBac (PDB: 6VWX, 6VX3, UniProt: Q9KCR8) that was purified using SEC in highly basic conditions with pH of 10 ( 34 ).…”

Section: Resultsmentioning

confidence: 99%

PurificationDB: database of purification conditions for proteins

et al. 2023

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The isolation of proteins of interest from cell lysates is an integral step to study protein structure and function. Liquid chromatography is a technique commonly used for protein purification, where the separation is performed by exploiting the differences in physical and chemical characteristics of proteins. The complex nature of proteins requires researchers to carefully choose buffers that maintain stability and activity of the protein while also allowing for appropriate interaction with chromatography columns. To choose the proper buffer, biochemists often search for reports of successful purification in the literature; however, they often encounter roadblocks such as lack of accessibility to journals, non-exhaustive specification of components and unfamiliar naming conventions. To overcome such issues, we present PurificationDB (https://purificationdatabase.herokuapp.com/), an open-access and user-friendly knowledge base that contains 4732 curated and standardized entries of protein purification conditions. Buffer specifications were derived from the literature using named-entity recognition techniques developed using common nomenclature provided by protein biochemists. PurificationDB also incorporates information associated with well-known protein databases: Protein Data Bank and UniProt. PurificationDB facilitates easy access to data on protein purification techniques and contributes to the growing effort of creating open resources that organize experimental conditions and data for improved access and analysis. Database URL https://purificationdatabase.herokuapp.com/

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“…All computational methods related to the electrostatic pipeline are detailed in [5,6,[9][10][11][12]. For the specific calculation of Electric Force, APBS returns a factor for in:…”

Section: Vw1_2mentioning

confidence: 99%

“…We have previously performed extensive research using electrostatic analysis of HIV gp120 envelope glycoprotein interactions with human CD4 and broadly neutralizing antibody proteins [5,6,[9][10][11][12]. Electrostatics are a novel way to evaluate protein interactions at the structural level with a focus on how environmental conditions, like pH, effect binding efficacy.…”

Section: Introductionmentioning

confidence: 99%

Computational Electrostatics Predict Variations in SARS-CoV-2 Spike and Human ACE2 Interactions

Morton

Phillips

2020

Preprint

Self Cite

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SARS-CoV-2 is a novel virus that is presumed to have emerged from bats to crossover into humans in late 2019. As the global pandemic ensues, scientist are working to evaluate the virus and develop a vaccine to counteract the deadly disease that has impacted lives across the entire globe. We perform computational electrostatic simulations on multiple variants of SARS-CoV-2 in complex with human angiotensin-converting enzyme 2 (ACE2) variants to examine differences in electrostatic interactions across the various complexes. Calculations are performed across the physiological pH range to also examine the impact of pH on these interactions. Two of six SARS-CoV-2 variations having greater electric forces at pH levels consistent with nasal secretions and significant variations in force across all five variants of ACE2. Five out of six SARS-CoV-2 variations have relatively consistent forces at pH levels of the lung, and one SARS-CoV-2 variant that has low potential across a wide range of pH. These predictions indicate that variants of SARS-CoV-2 and human ACE2 in certain combinations could potentially play a role in increased binding efficacy of SARS-CoV-2 in vivo.

show abstract

The Molecular Basis of pH-Modulated HIV gp120 Binding Revealed

Cited by 4 publications

References 32 publications

Computational Electrostatics Predict Variations in SARS-CoV-2 Spike and Human ACE2 Interactions

Computational Electrostatics Predict Variations in SARS-CoV-2 Spike and Human ACE2 Interactions

PurificationDB: database of purification conditions for proteins

Computational Electrostatics Predict Variations in SARS-CoV-2 Spike and Human ACE2 Interactions

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