A5083596284- Receptor Mechanisms and Signaling
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Computational Drug Discovery Methods
- Protein Structure and Dynamics
- Protein Kinase Regulation and GTPase Signaling
- Ferroelectric and Negative Capacitance Devices
- Mass Spectrometry Techniques and Applications
- Mitochondrial Function and Pathology
- Olfactory and Sensory Function Studies
- Neuroscience and Neuropharmacology Research
- Signaling Pathways in Disease
- Photosynthetic Processes and Mechanisms
- CRISPR and Genetic Engineering
- Traumatic Brain Injury and Neurovascular Disturbances
- Metabolism, Diabetes, and Cancer
- Biochemical Analysis and Sensing Techniques
- Blood disorders and treatments
- Cancer Mechanisms and Therapy
- ATP Synthase and ATPases Research
- interferon and immune responses
- Analytical Chemistry and Chromatography
- Neuropeptides and Animal Physiology
- RNA and protein synthesis mechanisms
- Neurobiology and Insect Physiology Research
Beckman Research Institute
2022-2025
City of Hope
2022-2025
The University of Texas Health Science Center at Houston
2023
Research Center of Neurology
2019
Lomonosov Moscow State University
2017
Abstract Recent studies have shown that G protein coupled receptors (GPCRs) show selective and promiscuous coupling to different Gα subfamilies yet the mechanisms of range preferences remain unclear. Here, we use Molecular Dynamics (MD) simulations on ten GPCR:G complexes location (spatial) duration (temporal) intermolecular contacts at GPCR:Gα interface play a critical role in how GPCRs selectively interact with proteins. We identify some are common across others specific subfamilies. Using...
Abstract The plasma membrane is enriched for receptors and signaling proteins that are accessible from the extracellular space pharmacological intervention. Here we conducted a series of CRISPR screens using human cell surface proteome integrin family libraries in multiple cancer models. Our results identified ITGAV (integrin αV) its heterodimer partner ITGB5 β5) as essential α/β pair expansion. High-density gene tiling further pinpointed integral pocket within β-propeller domain αVβ5...
Epigenetic dysregulation has been reported in multiple cancers including leukemias. Nonetheless, the roles of epigenetic reader Tudor domains leukemia progression and therapy remain unexplored. Here, we conducted a domain–focused CRISPR screen identified SGF29, component SAGA/ATAC acetyltransferase complexes, as crucial factor for H3K9 acetylation, ribosomal gene expression, leukemogenesis. To facilitate drug development, integrated tiling scan with compound docking molecular dynamics...
There are two main families of G protein-coupled receptors that detect odours in humans, the odorant (ORs) and trace amine-associated (TAARs). Their amino acid sequences distinct, with TAARs being most similar to aminergic such as those activated by adrenaline, serotonin, dopamine histamine. To elucidate structural determinants ligand recognition TAARs, we have determined cryo-EM structure a murine receptor, mTAAR7f, coupled heterotrimeric protein
Bayesian network modeling (BN modeling, or BNM) is an interpretable machine learning method for constructing probabilistic graphical models from the data. In recent years, it has been extensively applied to diverse types of biomedical data sets. Concurrently, our ability perform long-time scale molecular dynamics (MD) simulations on proteins and other materials increased exponentially. However, analysis MD simulation trajectories not data-driven but rather dependent user's prior knowledge...
Strong ligand directed degraders stabilize the hydrophobic residue burial between E3 ligase and target protein to be degraded. Weak destabilize ternary complex through multiple mechanisms.
Abstract PROteolysis TArgeting Chimeras (PROTACs), also known as Ligand-Directed Degraders (LDDs), are an innovative class of small molecules that leverage the ubiquitin-proteasome system to induce degradation target proteins. Structure based design methods not readily applicable for designing LDDs due dynamic nature ternary complexes. This study investigates properties five LDD-mediated BRD4-Cereblon complexes, focusing on challenges evaluating linker efficiency difficulty in identifying...
Identifying target-specific drugs remains a challenge in pharmacology, especially for highly homologous proteins such as dopamine receptors D2R and D3R. Differences cryptic druggable sites arise from the distinct conformational ensembles underlying their dynamic behavior. While Molecular Dynamics (MD) simulations has emerged powerful tool dissecting protein dynamics, sheer volume of MD data requires scalable unbiased analysis strategies to pinpoint residue communities regulating state...
Bayesian network modeling (BN modeling, or BNM) is an interpretable machine learning method for constructing probabilistic graphical models from the data. In recent years, it has been extensively applied to diverse types of biomedical datasets. Concurrently, our ability perform long-timescale molecular dynamics (MD) simulations on proteins and other materials increased exponentially. However, analysis MD simulation trajectories not data-driven but rather dependent user's prior knowledge...
There are two main families of G protein-coupled receptors that detect odours in humans, the odorant (ORs) and trace amine-associated (TAARs). Their amino acid sequences distinct, with TAARs being most similar to aminergic such as those activated by adrenaline, serotonin histamine. To elucidate structural determinants ligand recognition TAARs, we have determined cryo-EM structure a murine receptor, mTAAR7f, coupled heterotrimeric protein
Abstract Highly homologous members of the Gα i family, i1-3 , have distinct tissue distributions and physiological functions, yet functional properties these proteins with respect to GDP/GTP binding regulation adenylate cyclase are very similar. We recently identified PDZ-RhoGEF (PRG) as a novel i1 effector, however, it is poorly activated by i2 . Here, in proteomic proximity labeling screen we observed strong preference for relative engagement broad range potential targets. investigated...
Abstract Cooperative interactions in protein-protein interfaces demonstrate the interdependency or linked network-like behavior of interface and their effect on coupling proteins. also could cause ripple allosteric effects at a distance interfaces. Although they are critically important it is challenging to determine which amino acid pair cooperative. In this work we have used Bayesian network modeling, an interpretable machine learning method, combined with molecular dynamics trajectories...
Abstract The structurally disordered intracellular loops (ICLs) of G protein-coupled receptors (GPCRs) play a critical role in protein coupling. In our previous work, we used combination FRET-based and computational methodologies to show that the third loop (ICL3) modulates activity coupling selectivity GPCRs. current study, have uncovered several lipid components modulating conformational ensemble ICL3 β2-adrenergic receptor (β2AR). Our findings indicate phosphatidylinositol...