A5023680912- RNA and protein synthesis mechanisms
- SARS-CoV-2 and COVID-19 Research
- RNA modifications and cancer
- Protein Structure and Dynamics
- Influenza Virus Research Studies
- DNA and Nucleic Acid Chemistry
- Immunotherapy and Immune Responses
- Enzyme Structure and Function
- Genomics and Phylogenetic Studies
- Monoclonal and Polyclonal Antibodies Research
- Bacteriophages and microbial interactions
- Endoplasmic Reticulum Stress and Disease
- Bacterial Genetics and Biotechnology
- Bacillus and Francisella bacterial research
- Viral Infections and Outbreaks Research
- Electrohydrodynamics and Fluid Dynamics
- Advanced biosensing and bioanalysis techniques
- Amino Acid Enzymes and Metabolism
- Evolution and Genetic Dynamics
- Viral Infections and Immunology Research
- Lipid Membrane Structure and Behavior
- Heat shock proteins research
- Electrowetting and Microfluidic Technologies
- Gene Regulatory Network Analysis
- vaccines and immunoinformatics approaches
Cresset (United Kingdom)
2025
Los Alamos National Laboratory
2020-2023
Case Western Reserve University
2023
Northeastern University
2015-2020
Dana (United States)
2016
Symmetrization of contacts in D614G SARS-CoV-2 Spike favors greater probability infection-capable conformation.
Abstract Translocation of mRNA and tRNA through the ribosome is associated with large-scale rearrangements head domain in 30S ribosomal subunit. To elucidate relationship between dynamics mRNA–tRNA displacement, we apply molecular simulations using an all-atom structure-based model. Here provide a statistical analysis 250 spontaneous transitions A/P–P/E P/P–E/E ensembles. Consistent structural studies, samples chimeric ap/P–pe/E intermediate, where rotated ∼18°. It then transiently populates...
Summary The COVID-19 pandemic underwent a rapid transition with the emergence of SARS-CoV-2 variant that carried amino acid substitution D614G in Spike protein became globally prevalent. G-form is both more infectious vitro and associated increased viral loads infected people. To gain insight into mechanism underlying these distinctive characteristics, we employed multiple replicas microsecond all-atom simulations to probe molecular-level impact this on Spike’s closed open states. state...
Interdependence across time and length scales is common in biology, where atomic interactions can impact larger-scale phenomenon. Such dependence especially true for a well-known cancer signaling pathway, the membrane-bound RAS protein binds an effector called RAF. To capture driving forces that bring RAF (represented as two domains, RBD CRD) together on plasma membrane, simulations with ability to calculate detail while having long large length- are needed. The Multiscale Machine-Learned...
COVID-19 is a highly infectious respiratory disease caused by the novel coronavirus SARS-CoV-2. It has become global pandemic and its frequent mutations may pose new challenges for vaccine design. During viral infection, Spike RBD of SARS-CoV-2 binds human host cell receptor ACE2, enabling virus to enter cell. Both ACE2 are densely glycosylated, it unclear how distinctive glycan types modulate interaction ACE2. Detailed understanding these determinants key development therapeutic strategies....
Protein synthesis by the ribosome requires large-scale rearrangements of 'small' subunit (SSU; ∼1 MDa), including inter- and intra-subunit rotational motions. However, with nearly 2000 structures ribosomes ribosomal subunits now publicly available, it is exceedingly difficult to design experiments based on analysis all known rotation states. To overcome this, we developed an approach where orientation each SSU head body described in terms three angular coordinates (rotation, tilt direction)...
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, generates multiple protein-coding, subgenomic RNAs (sgRNAs) from a longer genomic RNA, all bearing identical termini with poorly understood roles in regulating viral gene expression. Insulin and interferon-gamma, two host-derived, stress-related agents, virus spike protein, induce binding glutamyl-prolyl-tRNA synthetase (EPRS1), within an unconventional, tetra-aminoacyl-tRNA complex, to...
The SARS-CoV-2 Spike glycoprotein is central to viral infectivity and immune evasion, making it a key target for vaccine therapeutic design. This trimeric peplomer undergoes dynamic conformational changes, particularly in its Receptor Binding Domain (RBD), which transitions between closed (down) ACE2-accessible (up) states relative the rest of protein, facilitate host cell entry. Structural understanding such critical inter-domain motions, as well epitope exposure quantification, essential...
As our understanding of biological dynamics continues to be refined, it is becoming clear that biomolecules can undergo transitions between ordered and disordered states as they execute functional processes. From a computational perspective, studying disorder events poses challenge, typically occur on long timescales, the associated molecules are often large (i.e., hundreds residues). These size time requirements make advantageous use computationally inexpensive models characterize...
The appeal of multiscale modeling approaches is predicated on the promise combinatorial synergy. However, this can only be realized when distinct scales are combined with reciprocal consistency. Here, we consider molecular dynamics (MD) simulations that combine accuracy and macromolecular flexibility accessible to fixed-charge all-atom (AA) representations sampling speed reductive, coarse-grained (CG) representations. AA-to-CG conversions relatively straightforward because deterministic...
Proteins are synthesized by the joint action of ribosome and tRNA molecules, where rate synthesis can be affected numerous factors, such as concentration tRNA, binding affinity for ribosome, or post-transcriptional modifications. Here, we expand this range contributors demonstrating how differences in structure give rise to species-specific dynamics ribosome. To show this, perform simulations A/P hybrid-state formation two species (tRNAPhe tRNALeu), which differ size their variable loops...
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has triggered myriad efforts to understand structure and dynamics of this complex pathogen. spike glycoprotein is a significant target for immunogens as it means which virus enters human cells, while simultaneously sporting mutations responsible immune escape. These functional escape processes are regulated molecular-level interactions. Our study presents quantitative insights on domain residue contributions allosteric communication,...
In order to quantitatively describe the energetics of biomolecular rearrangements, it is necessary identify reaction coordinates that accurately capture relevant transition events. Here, we perform simulations A-site tRNA movement (∼20 Å) during hybrid-state formation in ribosome and quantify ability interatomic distances state ensemble. Numerous are found be accurate indicators state, allowing rearrangements described as diffusion across a one-dimensional free-energy surface. addition...
Understanding how enzymes achieve their tremendous catalytic power is a major question in biochemistry. Greater understanding also needed for enzyme engineering applications. In many cases, efficiency and specificity depend on residues not direct contact with the substrate, termed remote residues. This work focuses Escherichia coli ornithine transcarbamoylase (OTC), which plays central role amino acid metabolism. OTC has been reported to undergo an induced-fit conformational change upon...
Abstract COVID-19 is a highly infectious respiratory disease caused by the novel coronavirus SARS-CoV-2. It has become global pandemic and its frequent mutations may pose new challenges for vaccine design. During viral infection, Spike RBD of SARS-CoV-2 binds human host cell receptor ACE2, enabling virus to enter cell. Both ACE2 are densely glycosylated, it unclear how distinctive glycan types modulate interaction ACE2. Detailed understanding these determinants key development therapeutic...
Abstract Protein synthesis by the ribosome involves large-scale rearrangements of “small” subunit (SSU; ∼1 MDa), which include inter- and intra-subunit rotational motions. With more than 1000 structures ribosomes ribosomal subunits now publicly available, it is becoming increasingly difficult to design precise experiments that are based on a comprehensive analysis all known rotation states. To overcome this limitation, we present Ribosome Angle Decomposition (RAD) method, where orientation...
The ribosome is a massive molecular complex that undergoes large-scale rotary motions during the translocation step of protein synthesis. During translocation, tRNA molecules move (along with mRNA) by one binding site (∼20-50A displacement), in order to allow next mRNA codon be decoded. To illuminate physical relationship between movement tRNAs and rotations ribosome, we applied dynamics (MD) simulations an all-atom structure-based model. By using model contains simplified description...