A5014353411- Microtubule and mitosis dynamics
- Genomics and Chromatin Dynamics
- Plant Molecular Biology Research
- RNA Research and Splicing
- Biofuel production and bioconversion
- Drug Transport and Resistance Mechanisms
- Bacteriophages and microbial interactions
- Computational Drug Discovery Methods
- Trace Elements in Health
- Photosynthetic Processes and Mechanisms
- Legume Nitrogen Fixing Symbiosis
- Alzheimer's disease research and treatments
- 14-3-3 protein interactions
- biodegradable polymer synthesis and properties
- Glycosylation and Glycoproteins Research
The University of Texas Southwestern Medical Center
2021-2024
Southern Methodist University
2021-2024
Pennsylvania State University
2023
Center for Systems Biology
2021
P-glycoprotein (P-gp) is a critical membrane transporter in the blood brain barrier (BBB) and implicated Alzheimer's disease (AD). However, previous studies on ability of P-gp to directly transport associated amyloid-β (Aβ) protein have produced contradictory results. Here we use molecular dynamics (MD) simulations, substrate accumulation cell culture, biochemical activity assays show that actively transports Aβ. We observed Aβ40 Aβ42 monomers by explicit MD simulations putative catalytic...
Microtubule polymerization dynamics result from the biochemical interactions of αβ-tubulin with polymer end, but a quantitative understanding has been challenging to establish. We used interference reflection microscopy make improved measurements microtubule growth rates and fluctuations in presence absence GTP hydrolysis. In hydrolysis, microtubules grew steadily very low fluctuations. These data were best described by computational model implementing slow assembly kinetics, such that rate...
GTP-tubulin is preferentially incorporated at growing microtubule ends, but the biochemical mechanism by which bound nucleotide regulates strength of tubulin:tubulin interactions debated. The 'self-acting' (cis) model posits that (GTP or GDP) to a particular tubulin dictates how strongly interacts, whereas 'interface-acting' (trans) interface two dimers determinant. We identified testable difference between these mechanisms using mixed simulations elongation: with self-acting nucleotide,...
GTP-tubulin is preferentially incorporated at growing microtubule ends, but the biochemical mechanism by which bound nucleotide regulates strength of tubulin:tubulin interactions debated. The ‘self-acting’ (cis) model posits that (GTP or GDP) to a particular tubulin dictates how strongly interacts, whereas ‘interface-acting’ (trans) interface two dimers determinant. We identified testable difference between these mechanisms using mixed simulations elongation: with self-acting nucleotide,...
Abstract Overexpression of the polyspecific efflux transporter, P-glycoprotein (P-gp, MDR1, ABCB1 ), is a major mechanism by which cancer cells acquire multidrug resistance (MDR), to diverse chemotherapeutic drugs. Inhibiting drug transport P-gp can resensitize chemotherapy, but there are no inhibitors available patients. Clinically unsuccessful tend bind at pump’s transmembrane binding domains and often substrates, resulting in lowered intracellular concentration altered pharmacokinetics....
Abstract GTP-tubulin is preferentially incorporated at growing microtubule ends, but the biochemical mechanism by which bound nucleotide regulates strength of tubulin:tubulin interactions debated. The ‘self-acting’ (cis) model posits that (GTP or GDP) to a particular tubulin dictates how strongly interacts, whereas ‘interface-acting’ (trans) interface two dimers determinant. We identified testable difference between these mechanisms using mixed simulations elongation: with self-acting...
Abstract GTP-tubulin is preferentially incorporated at growing microtubule ends, but the biochemical mechanism by which bound nucleotide regulates strength of tubulin:tubulin interactions debated. The ‘self-acting’ (cis) model posits that (GTP or GDP) to a particular tubulin dictates how strongly interacts, whereas ‘interface-acting’ (trans) interface two dimers determinant. We identified testable difference between these mechanisms using mixed simulations elongation: with self-acting plus-...
GTP-tubulin is preferentially incorporated at growing microtubule ends, but the biochemical mechanism by which bound nucleotide regulates strength of tubulin:tubulin interactions debated. The ‘self-acting’ (cis) model posits that (GTP or GDP) to a particular tubulin dictates how strongly interacts, whereas ‘interface-acting’ (trans) interface two dimers determinant. We identified testable difference between these mechanisms using mixed simulations elongation: with self-acting nucleotide,...