Alexander Grishaev
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View article: Conformational dynamics and multimodal interaction of Paxillin with the focal adhesion targeting domain
Conformational dynamics and multimodal interaction of Paxillin with the focal adhesion targeting domain Open
Paxillin (PXN) and focal adhesion kinase (FAK) are two major components of the focal adhesion complex, a multiprotein structure linking the intracellular cytoskeleton to the cell exterior. The interaction between the disordered amino-termi…
View article: Critical Assessment of RNA and DNA Structure Predictions via Artificial Intelligence: The Imitation Game
Critical Assessment of RNA and DNA Structure Predictions via Artificial Intelligence: The Imitation Game Open
Computational predictions of biomolecular structure via artificial intelligence (AI) based approaches, as exemplified by AlphaFold software, have the potential to model of all life's biomolecules. We performed oligonucleotide structure pre…
View article: Conformational dynamics and multi-modal interaction of Paxillin with the Focal Adhesion Targeting Domain
Conformational dynamics and multi-modal interaction of Paxillin with the Focal Adhesion Targeting Domain Open
Paxillin (PXN) and focal adhesion kinase (FAK) are two major components of the focal adhesion complex, a multiprotein structure linking the intracellular cytoskeleton to the cell exterior. The interaction between the disordered N-terminal …
View article: Anisotropic coarse-grain Monte Carlo simulations of lysozyme, lactoferrin, and NISTmAb by precomputing atomistic models
Anisotropic coarse-grain Monte Carlo simulations of lysozyme, lactoferrin, and NISTmAb by precomputing atomistic models Open
We develop a multiscale coarse-grain model of the NIST Monoclonal Antibody Reference Material 8671 (NISTmAb) to enable systematic computational investigations of high-concentration physical instabilities such as phase separation, clusterin…
View article: Extended <i>q</i>‐Range X‐Ray Scattering Reveals High‐Resolution Structural Details of Biomacromolecules in Aqueous Solutions
Extended <i>q</i>‐Range X‐Ray Scattering Reveals High‐Resolution Structural Details of Biomacromolecules in Aqueous Solutions Open
We communicate a feasibility study for high‐resolution structural characterization of biomacromolecules in aqueous solution from X‐ray scattering experiments measured over a range of scattering vectors ( q ) that is approximately two order…
View article: A round-robin approach provides a detailed assessment of biomolecular small-angle scattering data reproducibility and yields consensus curves for benchmarking
A round-robin approach provides a detailed assessment of biomolecular small-angle scattering data reproducibility and yields consensus curves for benchmarking Open
Through an expansive international effort that involved data collection on 12 small-angle X-ray scattering (SAXS) and four small-angle neutron scattering (SANS) instruments, 171 SAXS and 76 SANS measurements for five proteins (ribonuclease…
View article: Conformational heterogeneity of UCAAUC RNA oligonucleotide from molecular dynamics simulations, SAXS, and NMR experiments
Conformational heterogeneity of UCAAUC RNA oligonucleotide from molecular dynamics simulations, SAXS, and NMR experiments Open
We describe the conformational ensemble of the single-stranded r(UCAAUC) oligonucleotide obtained using extensive molecular dynamics (MD) simulations and Rosetta's FARFAR2 algorithm. The conformations observed in MD consist of A-form-like …
View article: Novel lipid nanoparticle provides potent SARS-CoV-2 mRNA vaccine at low dose with low local reactogenicity, high thermostability and limited systemic biodistribution
Novel lipid nanoparticle provides potent SARS-CoV-2 mRNA vaccine at low dose with low local reactogenicity, high thermostability and limited systemic biodistribution Open
Concerns with current mRNA Lipid Nanoparticle (LNP) systems include dose-limiting reactogenicity, adverse events that may be partly due to systemic off target expression of the immunogen, and a very limited understanding of the mechanisms …
View article: Ionization and structural properties of mRNA lipid nanoparticles influence expression in intramuscular and intravascular administration
Ionization and structural properties of mRNA lipid nanoparticles influence expression in intramuscular and intravascular administration Open
Lipid Nanoparticles (LNPs) are used to deliver siRNA and COVID-19 mRNA vaccines. The main factor known to determine their delivery efficiency is the pKa of the LNP containing an ionizable lipid. Herein, we report a method that can predict …
View article: Structural Characterization and Modeling of a Respiratory Syncytial Virus Fusion Glycoprotein Nanoparticle Vaccine in Solution
Structural Characterization and Modeling of a Respiratory Syncytial Virus Fusion Glycoprotein Nanoparticle Vaccine in Solution Open
The respiratory syncytial virus (RSV) fusion (F) protein/polysorbate 80 (PS80) nanoparticle vaccine is the most clinically advanced vaccine for maternal immunization and protection of newborns against RSV infection. It is composed of a nea…
View article: Chemical shifts-based similarity restraints improve accuracy of RNA structures determined via NMR
Chemical shifts-based similarity restraints improve accuracy of RNA structures determined via NMR Open
Determination of structure of RNA via NMR is complicated in large part by the lack of a precise parameterization linking the observed chemical shifts to the underlying geometric parameters. In contrast to proteins, where numerous high-reso…
View article: HIV-1 gp120–CD4-Induced Antibody Complex Elicits CD4 Binding Site–Specific Antibody Response in Mice
HIV-1 gp120–CD4-Induced Antibody Complex Elicits CD4 Binding Site–Specific Antibody Response in Mice Open
Elicitation of broadly neutralizing Ab (bNAb) responses toward the conserved HIV-1 envelope (Env) CD4 binding site (CD4bs) by vaccination is an important goal for vaccine development and yet to be achieved. The outcome of previous immunoge…
View article: Structure of the cell-binding component of the <i>Clostridium difficile</i> binary toxin reveals a di-heptamer macromolecular assembly
Structure of the cell-binding component of the <i>Clostridium difficile</i> binary toxin reveals a di-heptamer macromolecular assembly Open
Targeting Clostridium difficile infection is challenging because treatment options are limited, and high recurrence rates are common. One reason for this is that hypervirulent C. difficile strains often have a binary toxin termed the C. di…
View article: Structure of the cell-binding component of the<i>Clostridium difficile</i>binary toxin reveals a novel macromolecular assembly
Structure of the cell-binding component of the<i>Clostridium difficile</i>binary toxin reveals a novel macromolecular assembly Open
Targeting Clostridium difficile infection (CDI) is challenging because treatment options are limited, and high recurrence rates are common. One reason for this is that hypervirulent CDI often has a binary toxin termed the C. difficile toxi…
View article: Comment on “Innovative scattering analysis shows that hydrophobic disordered proteins are expanded in water”
Comment on “Innovative scattering analysis shows that hydrophobic disordered proteins are expanded in water” Open
Riback et al . (Reports, 13 October 2017, p. 238) used small-angle x-ray scattering (SAXS) experiments to infer a degree of compaction for unfolded proteins in water versus chemical denaturant that is highly consistent with the results fro…
View article: A trapped human PPM1A–phosphopeptide complex reveals structural features critical for regulation of PPM protein phosphatase activity
A trapped human PPM1A–phosphopeptide complex reveals structural features critical for regulation of PPM protein phosphatase activity Open
Metal-dependent protein phosphatases (PPM) are evolutionarily unrelated to other serine/threonine protein phosphatases and are characterized by their requirement for supplementation with millimolar concentrations of Mg2+ or Mn2+ ions for a…
View article: PAGE4 and Conformational Switching: Insights from Molecular Dynamics Simulations and Implications for Prostate Cancer
PAGE4 and Conformational Switching: Insights from Molecular Dynamics Simulations and Implications for Prostate Cancer Open
Prostate-Associated Gene 4 (PAGE4) is a disordered protein implicated in the progression of prostate cancer. PAGE4 can be phosphorylated at two residue sites by Homeodomain-Interacting Protein Kinase 1 (HIPK1) to facilitate its binding to …
View article: Prediction of nearest neighbor effects on backbone torsion angles and NMR scalar coupling constants in disordered proteins
Prediction of nearest neighbor effects on backbone torsion angles and NMR scalar coupling constants in disordered proteins Open
Using fine‐tuned hydrogen bonding criteria, a library of coiled peptide fragments has been generated from a large set of high‐resolution protein X‐ray structures. This library is shown to be an improved representation of ϕ/ψ torsion angles…
View article: Phosphorylation-induced conformational dynamics in an intrinsically disordered protein and potential role in phenotypic heterogeneity
Phosphorylation-induced conformational dynamics in an intrinsically disordered protein and potential role in phenotypic heterogeneity Open
Significance The onset of androgen resistance is a major impediment in treating prostate cancer (PCa). However, the underlying molecular mechanisms are not fully understood. Here, we integrate multiple biophysical approaches that report co…
View article: Probing the Action of Chemical Denaturant on an Intrinsically Disordered Protein by Simulation and Experiment
Probing the Action of Chemical Denaturant on an Intrinsically Disordered Protein by Simulation and Experiment Open
Chemical denaturants are the most commonly used agents for unfolding proteins and are thought to act by better solvating the unfolded state. Improved solvation is expected to lead to an expansion of unfolded chains with increasing denatura…
View article: Consistent View of Polypeptide Chain Expansion in Chemical Denaturants from Multiple Experimental Methods
Consistent View of Polypeptide Chain Expansion in Chemical Denaturants from Multiple Experimental Methods Open
There has been a long-standing controversy regarding the effect of chemical denaturants on the dimensions of unfolded and intrinsically disordered proteins: A wide range of experimental techniques suggest that polypeptide chains expand wit…
View article: Inside Back Cover: Quantitative Characterization of Configurational Space Sampled by HIV‐1 Nucleocapsid Using Solution NMR, X‐ray Scattering and Protein Engineering (ChemPhysChem 11/2016)
Inside Back Cover: Quantitative Characterization of Configurational Space Sampled by HIV‐1 Nucleocapsid Using Solution NMR, X‐ray Scattering and Protein Engineering (ChemPhysChem 11/2016) Open
The Inside Back Cover picture shows an unliganded HIV-1 nucleocapsid is investigated using solution NMR–residual dipolar couplings, small-angle X-ray scattering, and protein engineering, coupled with ensemble-simulated annealing. More info…
View article: Quantitative Characterization of Configurational Space Sampled by HIV‐1 Nucleocapsid Using Solution NMR, X‐ray Scattering and Protein Engineering
Quantitative Characterization of Configurational Space Sampled by HIV‐1 Nucleocapsid Using Solution NMR, X‐ray Scattering and Protein Engineering Open
Nucleic‐acid‐related events in the HIV‐1 replication cycle are mediated by nucleocapsid, a small protein comprising two zinc knuckles connected by a short flexible linker and flanked by disordered termini. Combining experimental NMR residu…
View article: Side Chain Conformational Distributions of a Small Protein Derived from Model-Free Analysis of a Large Set of Residual Dipolar Couplings
Side Chain Conformational Distributions of a Small Protein Derived from Model-Free Analysis of a Large Set of Residual Dipolar Couplings Open
Accurate quantitative measurement of structural dispersion in proteins remains a prime challenge to both X-ray crystallography and NMR spectroscopy. Here we use a model-free approach based on measurement of many residual dipolar couplings …
View article: Dynamic equilibrium between closed and partially closed states of the bacterial Enzyme I unveiled by solution NMR and X-ray scattering
Dynamic equilibrium between closed and partially closed states of the bacterial Enzyme I unveiled by solution NMR and X-ray scattering Open
Significance The bacterial phosphotransferase system couples phosphoryl transfer to sugar transport across the cell membrane. The first protein in the pathway, Enzyme I (EI), undergoes two large rigid body domain reorientations between an …