Kyle Mimun | Texas A&M University (original) (raw)
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University of Texas Health Science Center at San Antonio (UTHSCSA)
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Papers by Kyle Mimun
The comprehensive assignment of individual resonances of the nuclear magnetic resonance spectrum ... more The comprehensive assignment of individual resonances of the nuclear magnetic resonance spectrum of a protein to specific atoms remains a labor-intensive and often debilitating taskespecially for proteins larger than 30 kDa. Recently, there have been tremendous advances in our empirical knowledge of the relationship between the structural context of a nuclear spin and its observed resonance frequency. Indeed, the expansion in the database of determined highresolution protein structures and recent advances in structure prediction provide an enormous resource in this respect. Robust automation of the resonance assignment process nevertheless often remains a bottleneck in the exploitation of solution NMR spectroscopy for the study of protein structure-dynamics-function relationships. Here we present a new approach for the assignment of backbone triple resonance spectra of proteins. A Bayesian statistical analysis of predicted and observed chemical shifts is used to provide a pseudo-energy potential to drive the search for the most optimal set of resonance assignments. This approach has been implemented in the C++ program Bayllagio and tested against protein systems ranging in size to over 450 amino acids. Bayllagio makes almost no errors, accommodates incomplete information, is sufficiently fast to allow for real-time evaluation of data acquisition, and greatly outperforms currently employed deterministic algorithms.
Frontiers in Drug Delivery
Nicotine, the major component of tobacco smoke (TS) and electronic cigarette (e-cig) vape, has be... more Nicotine, the major component of tobacco smoke (TS) and electronic cigarette (e-cig) vape, has been reported in some cases to be prodromal to cerebrovascular toxicity as well as a promoting factor for the onset of various neurological diseases. In some conditions, pre-exposure to nicotine can lead to a state of compromised blood-brain barrier (BBB) integrity, including altered BBB-related protein expression, BBB leakage, and defective ion and glucose homeostasis within the brain. Moreover, drugs used to treat central nervous system disorders (CNS) have been reported to interact with nicotine and other components of TS/e-cig through both transporter and enzyme-based mechanisms. Herein we discuss nicotine’s potential toxicity at the brain cerebrovasculature and explain how nicotine (from smoking/vaping) may interfere with the uptake of CNS drugs through a CNS drug interaction perspective.
The comprehensive assignment of individual resonances of the nuclear magnetic resonance spectrum ... more The comprehensive assignment of individual resonances of the nuclear magnetic resonance spectrum of a protein to specific atoms remains a labor-intensive and often debilitating taskespecially for proteins larger than 30 kDa. Recently, there have been tremendous advances in our empirical knowledge of the relationship between the structural context of a nuclear spin and its observed resonance frequency. Indeed, the expansion in the database of determined highresolution protein structures and recent advances in structure prediction provide an enormous resource in this respect. Robust automation of the resonance assignment process nevertheless often remains a bottleneck in the exploitation of solution NMR spectroscopy for the study of protein structure-dynamics-function relationships. Here we present a new approach for the assignment of backbone triple resonance spectra of proteins. A Bayesian statistical analysis of predicted and observed chemical shifts is used to provide a pseudo-energy potential to drive the search for the most optimal set of resonance assignments. This approach has been implemented in the C++ program Bayllagio and tested against protein systems ranging in size to over 450 amino acids. Bayllagio makes almost no errors, accommodates incomplete information, is sufficiently fast to allow for real-time evaluation of data acquisition, and greatly outperforms currently employed deterministic algorithms.
Frontiers in Drug Delivery
Nicotine, the major component of tobacco smoke (TS) and electronic cigarette (e-cig) vape, has be... more Nicotine, the major component of tobacco smoke (TS) and electronic cigarette (e-cig) vape, has been reported in some cases to be prodromal to cerebrovascular toxicity as well as a promoting factor for the onset of various neurological diseases. In some conditions, pre-exposure to nicotine can lead to a state of compromised blood-brain barrier (BBB) integrity, including altered BBB-related protein expression, BBB leakage, and defective ion and glucose homeostasis within the brain. Moreover, drugs used to treat central nervous system disorders (CNS) have been reported to interact with nicotine and other components of TS/e-cig through both transporter and enzyme-based mechanisms. Herein we discuss nicotine’s potential toxicity at the brain cerebrovasculature and explain how nicotine (from smoking/vaping) may interfere with the uptake of CNS drugs through a CNS drug interaction perspective.