BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

“Bioinformatics” 특집을 내면서

인공고관절의 세라믹 볼 헤드의 기계적 안정성 평가를 위한 3 차원 유한요소 해석

Molecular docking has become an increasingly important tool for drug discovery. In this review, we present a brief introduction of the available molecular docking methods, and their development and applications in drug discovery. The relevant basic theories, including sampling algorithms and scoring functions, are summarized. The differences in and performance of available docking software are also discussed. Flexible receptor molecular docking approaches, especially those including backbone flexibility in receptors, are a challenge for available docking methods. A recently developed Local Move Monte Carlo (LMMC) based approach is introduced as a potential solution to flexible receptor docking problems. Three application examples of molecular docking approaches for drug discovery are provided.

/pdf/molecular-docking-a-powerful-approach-for-structure-based-3scyz9zmai.pdf

Molecular docking: a powerful approach for structure-based drug discovery.

Computer-aided drug discovery/design methods have played a major role in the development of therapeutically important small molecules for over three decades. These methods are broadly classified as either structure-based or ligand-based methods. Structure-based methods are in principle analogous to high-throughput screening in that both target and ligand structure information is imperative. Structure-based approaches include ligand docking, pharmacophore, and ligand design methods. The article discusses theory behind the most important methods and recent successful applications. Ligand-based methods use only ligand information for predicting activity depending on its similarity/dissimilarity to previously known active ligands. We review widely used ligand-based methods such as ligand-based pharmacophores, molecular descriptors, and quantitative structure-activity relationships. In addition, important tools such as target/ligand data bases, homology modeling, ligand fingerprint methods, etc., necessary for successful implementation of various computer-aided drug discovery/design methods in a drug discovery campaign are discussed. Finally, computational methods for toxicity prediction and optimization for favorable physiologic properties are discussed with successful examples from literature.

/pdf/computational-methods-in-drug-discovery-3sww6kbvd5.pdf

Computational Methods in Drug Discovery

The emerging picture of taste coding at the periphery is one of elegant simplicity. Contrary to what was generally believed, it is now clear that distinct cell types expressing unique receptors are tuned to detect each of the five basic tastes: sweet, sour, bitter, salty and umami. Importantly, receptor cells for each taste quality function as dedicated sensors wired to elicit stereotypic responses.

The receptors and cells for mammalian taste

Lactisole Interacts with the Transmembrane Domains of Human T1R3 to Inhibit Sweet Taste

Identification of the cyclamate interaction site within the transmembrane domain of the human sweet taste receptor subunit T1R3.

The sweet taste receptor is a heterodimer of two G protein coupled receptors, T1R2 and T1R3. This discovery has increased our understanding at the molecular level of the mechanisms underlying sweet taste. Previous experimental studies using sweet receptor chimeras and mutants show that there are at least three potential binding sites in this heterodimeric receptor. Receptor activity toward the artificial sweeteners aspartame and neotame depends on residues in the amino terminal domain of human T1R2. In contrast, receptor activity toward the sweetener cyclamate and the sweet taste inhibitor lactisole depends on residues within the transmembrane domain of human T1R3. Furthermore, receptor activity toward the sweet protein brazzein depends on the cysteine rich domain of human T1R3. Although crystal structures are not available for the sweet taste receptor, useful homology models can be developed based on appropriate templates. The amino terminal domain, cysteine rich domain and transmembrane helix domain of T1R2 and T1R3 have been modeled based on the crystal structures of metabotropic glutamate receptor type 1, tumor necrosis factor receptor, and bovine rhodopsin, respectively. We have used homology models of the sweet taste receptors, molecular docking of sweet ligands to the receptors, and site-directed mutagenesis of the receptors to identify potential ligand binding sites of the sweet taste receptor. These studies have led to a better understanding of the structure and function of this heterodimeric receptor, and can act as a guide for rational structure-based design of novel non-caloric sweeteners, which can be used in the fighting against obesity and diabetes.

The heterodimeric sweet taste receptor has multiple potential ligand binding sites.

Synthesis of liquid fuels (C 5+ hydrocarbons) via CO 2 hydrogenation is very promising. Hydrogenation of CO 2 to liquid hydrocarbons usually proceeds through tandem catalysis of reverse water gas shift (RWGS) reaction to produce CO, and subsequent CO hydrogenation to hydrocarbons via Fischer–Tropsch synthesis (FTS). CO 2 is a thermodynamically stable and chemically inert molecule, and RWGS reaction is endothermic and needs a higher temperature, whereas FTS reaction is exothermic and is thermodynamically favored at a lower temperature. Therefore, the reported technologies have some obvious drawbacks, such as high temperature, low selectivity, and use of complex catalysts. Herein we discovered that a simple Co 6 /MnO x nanocatalyst could efficiently catalyze CO 2 hydrogenation. The reaction proceeded at 200 °C, which is much lower than those reported so far. The selectivity of liquid hydrocarbon (C 5 to C 26 , mostly n -paraffin) in total product could reach 53.2 C-mol%, which is among the highest reported to date. Interestingly, CO was hardly detectable during the reaction. The in situ Fourier transform infrared characterization and 13 CO labeling test confirmed that the reaction was not via CO, accounting for the eminent catalytic results. This report represents significant progress in CO 2 chemistry and CO 2 transformation.

https://www.pnas.org/content/pnas/116/26/12654.full.pdf

Meng Cui

Papers

Molecular docking: a powerful approach for structure-based drug discovery.

Lactisole Interacts with the Transmembrane Domains of Human T1R3 to Inhibit Sweet Taste

Identification of the cyclamate interaction site within the transmembrane domain of the human sweet taste receptor subunit T1R3.

The heterodimeric sweet taste receptor has multiple potential ligand binding sites.

Synthesis of liquid fuel via direct hydrogenation of CO2