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Full-Text Articles in Physical Sciences and Mathematics
Mechanism Of Thermal Protein Aggregation: Experiments And Molecular Dynamics Simulations On The High-Temperature Behavior Of Myoglobin., Yuen Ki Ng, Nastaran N Tajoddin, Pablo M Scrosati, Lars Konermann
Mechanism Of Thermal Protein Aggregation: Experiments And Molecular Dynamics Simulations On The High-Temperature Behavior Of Myoglobin., Yuen Ki Ng, Nastaran N Tajoddin, Pablo M Scrosati, Lars Konermann
Chemistry Publications
Proteins that encounter unfavorable solvent conditions are prone to aggregation, a phenomenon that remains poorly understood. This work focuses on myoglobin (Mb) as a model protein. Upon heating, Mb produces amorphous aggregates. Thermal unfolding experiments at low concentration (where aggregation is negligible), along with centrifugation assays, imply that Mb aggregation proceeds via globally unfolded conformers. This contrasts studies on other proteins that emphasized the role of partially folded structures as aggregate precursors. Molecular dynamics (MD) simulations were performed to gain insights into the mechanism by which heat-unfolded Mb molecules associate with one another. A prerequisite for these simulations was the …
Analysis Of Temperature-Dependent H/D Exchange Mass Spectrometry Experiments., Nastaran N Tajoddin, Lars Konermann
Analysis Of Temperature-Dependent H/D Exchange Mass Spectrometry Experiments., Nastaran N Tajoddin, Lars Konermann
Chemistry Publications
H/D exchange (HDX) mass spectrometry (MS) is a widely used technique for interrogating protein structure and dynamics. Backbone HDX is mediated by opening/closing (unfolding/refolding) fluctuations. In traditional HDX-MS, proteins are incubated in D2O as a function of time at constant temperature (T). There is an urgent need to complement this traditional approach with experiments that probe proteins in a T-dependent fashion, e.g., for assessing the stability of therapeutic antibodies. A key problem with such studies is the absence of strategies for interpreting HDX-MS data in the context of T-dependent protein dynamics. Specifically, it has …
Enhancing Protein Electrospray Charge States By Multivalent Metal Ions: Mechanistic Insights From Md Simulations And Mass Spectrometry Experiments., Leanne M Martin, Lars Konermann
Enhancing Protein Electrospray Charge States By Multivalent Metal Ions: Mechanistic Insights From Md Simulations And Mass Spectrometry Experiments., Leanne M Martin, Lars Konermann
Chemistry Publications
The structure and reactivity of electrosprayed protein ions is governed by their net charge. Native proteins in non-denaturing aqueous solutions produce low charge states. More highly charged ions are formed when electrospraying proteins that are unfolded and/or exposed to organic supercharging agents. Numerous studies have explored the electrospray process under these various conditions. One phenomenon that has received surprisingly little attention is the charge enhancement caused by multivalent metal ions such as La3+ when electrospraying proteins out of non-denaturing solutions. Here, we conducted mass spectrometry and ion mobility spectrometry experiments, in combination with molecular dynamics (MD) simulations, to uncover …
Testing The Robustness Of Solution Force Fields For Md Simulations On Gaseous Protein Ions., Justin H Lee, Katja Pollert, Lars Konermann
Testing The Robustness Of Solution Force Fields For Md Simulations On Gaseous Protein Ions., Justin H Lee, Katja Pollert, Lars Konermann
Chemistry Publications
It is believed that electrosprayed proteins and protein complexes can retain solution-like conformations in the gas phase. However, the lack of high-resolution structure determination methods for gaseous protein ions implies that their properties remain poorly understood. Many practitioners tackle this difficulty by complementing mass spectrometry-based experiments with molecular dynamics (MD) simulations. It is a potential problem that the standard MD force fields used for this purpose (such as OPLS-AA/L and CHARMM) were optimized for solution conditions. The question whether these force fields produce meaningful gas-phase data has received surprisingly little attention. Standard force fields are overpolarized to account for an …
Mechanism Of Electrospray Supercharging For Unfolded Proteins: Solvent-Mediated Stabilization Of Protonated Sites During Chain Ejection., Insa Peters, Haidy Metwally, Lars Konermann
Mechanism Of Electrospray Supercharging For Unfolded Proteins: Solvent-Mediated Stabilization Of Protonated Sites During Chain Ejection., Insa Peters, Haidy Metwally, Lars Konermann
Chemistry Publications
Proteins that are unfolded in solution produce higher charge states during electrospray ionization (ESI) than their natively folded counterparts. Protein charge states can be further increased by the addition of supercharging agents (SCAs) such as sulfolane. The mechanism whereby these supercharged [M + zH] z+ ions are formed under unfolded conditions remains unclear. Here we employed a combination of mass spectrometry (MS), ion mobility spectrometry (IMS), and molecular dynamics (MD) simulations for probing the ESI mechanism under denatured supercharging conditions. ESI of acid-unfolded apo-myoglobin (aMb) in the presence of sulfolane produced charge states around 27+, all the way to fully …
Chain Ejection Model For Electrospray Ionization Of Unfolded Proteins: Evidence From Atomistic Simulations And Ion Mobility Spectrometry., Haidy Metwally, Quentin Duez, Lars Konermann
Chain Ejection Model For Electrospray Ionization Of Unfolded Proteins: Evidence From Atomistic Simulations And Ion Mobility Spectrometry., Haidy Metwally, Quentin Duez, Lars Konermann
Chemistry Publications
The ion evaporation model (IEM) and the charged residue model (CRM) represent cornerstones of any discussion related to the mechanism of electrospray ionization (ESI). Molecular dynamics (MD) simulations have confirmed that small ions such as Na+ are ejected from the surface of aqueous ESI droplets (IEM), while folded proteins in native ESI are released by water evaporation to dryness (CRM). ESI of unfolded proteins yields [M + zH] z+ ions that are much more highly charged than their folded counterparts. A chain ejection model (CEM) has been proposed to account for the protein ESI behavior under such non-native conditions …
Crown Ether Effects On The Location Of Charge Carriers In Electrospray Droplets: Implications For The Mechanism Of Protein Charging And Supercharging., Haidy Metwally, Lars Konermann
Crown Ether Effects On The Location Of Charge Carriers In Electrospray Droplets: Implications For The Mechanism Of Protein Charging And Supercharging., Haidy Metwally, Lars Konermann
Chemistry Publications
"Native" electrospray ionization (ESI) mass spectrometry (MS) aims to transfer proteins from solution into the gas phase while maintaining solution-like structures and interactions. The ability to control the charge states of protein ions produced in these experiments is of considerable importance. Supercharging agents (SCAs) such as sulfolane greatly elevate charge states without significantly affecting the protein structure in bulk aqueous solution. The origin of native ESI supercharging remains contentious. According to one model, SCAs trigger unfolding within ESI droplets. In contrast, the "charge trapping model" envisions that SCAs impede the ejection of charge carriers (e.g., NH4+ or Na …