scholarly journals Modulation of inherent dynamical tendencies of the bisabolyl cation via preorganization in epi-isozizaene synthase

2015 ◽  
Vol 6 (4) ◽  
pp. 2347-2353 ◽  
Author(s):  
Ryan P. Pemberton ◽  
Krystina C. Ho ◽  
Dean J. Tantillo
Keyword(s):  
Quantum Chemical ◽  
Product Distribution ◽  
Terpene Synthase ◽  
Chemical Dynamics ◽  
Relative Importance ◽  
Docking Calculations ◽  
Automated Docking

The relative importance of various factors controlling the product distribution for a terpene synthase are elucidated through a combination of quantum chemical, dynamics and automated docking calculations.

Inherent dynamical preferences in carbocation rearrangements leading to terpene natural products

2013 ◽  
Vol 85 (10) ◽  
pp. 1949-1957 ◽  
Author(s):  
Ryan P. Pemberton ◽  
Young J. Hong ◽  
Dean J. Tantillo
Keyword(s):  
Natural Products ◽  
Quantum Chemical ◽  
Chemical Dynamics ◽  
Terpene Biosynthesis ◽  
Bare Bones

An introduction to the application of quantum chemical dynamics calculations to mechanistic problems in the field of terpene biosynthesis is provided. A bare bones introduction to the fundamentals of chemical dynamics is followed by a brief account of previous applications to terpene-forming carbocation reactions, a discussion of questions in this field that dynamics calculations may help answer, and a description of current problems to which dynamics calculations are being applied.

scholarly journals Continuous Evaluation of Ligand Protein Predictions: A Weekly Community Challenge for Drug Docking

2018 ◽  
Author(s):  
Jeffrey R. Wagner ◽  
Christopher P. Churas ◽  
Shuai Liu ◽  
Robert V. Swift ◽  
Michael Chiu ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Drug Design ◽  
Ligand Binding ◽  
Unmet Need ◽  
Specific Protein ◽  
Protein Targets ◽  
Continuous Evaluation ◽  
Docking Algorithm ◽  
Docking Calculations ◽  
Automated Docking

1SummaryDocking calculations can be used to accelerate drug discovery by providing predictions of the poses of candidate ligands bound to a targeted protein. However, studies in the literature use varied docking methods, and it is not clear which work best, either in general or for specific protein targets. In addition, a complete docking calculation requires components beyond the docking algorithm itself, such as preparation of the protein and ligand for calculations, and it is difficult to isolate which aspects of a method are most in need of improvement. To address such issues, we have developed the Continuous Evaluation of Ligand Protein Predictions (CELPP), a weekly blinded challenge for automated docking workflows. Participants in CELPP create a workflow to predict protein-ligand binding poses, which is then tasked with predicting 10-100 new (never before released) protein-ligand crystal structures each week. CELPP evaluates the accuracy of each workflow’s predictions and posts the scores online. CELPP is a new cyberinfrastructure resource to identify the strengths and weaknesses of current approaches, help map docking problems to the algorithms most likely to overcome them, and illuminate areas of unmet need in structure-guided drug design.

scholarly journals Estimation of Inhibitory Effect against Tyrosinase Activity through Homology Modeling and Molecular Docking

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Daungkamon Nokinsee ◽  
Lalida Shank ◽  
Vannajan Sanghiran Lee ◽  
Piyarat Nimmanpipug
Keyword(s):  
Md Simulation ◽  
Inhibitory Effect ◽  
Human Model ◽  
Mushroom Tyrosinase ◽  
Whitening Agent ◽  
Human Enzyme ◽  
Cosmetic Industry ◽  
Key Enzyme ◽  
Docking Calculations ◽  
Automated Docking

Tyrosinase is a key enzyme in melanogenesis. Generally, mushroom tyrosinase from A. bisporus had been used as a model in skin-whitening agent tests employed in the cosmetic industry. The recently obtained crystal structure of bacterial tyrosinase from B. megaterium has high similarity (33.5%) to the human enzyme and thus it was used as a template for constructing of the human model. Binding of tyrosinase to a series of its inhibitors was simulated by automated docking calculations. Docking and MD simulation results suggested that N81, N260, H263, and M280 are involved in the binding of inhibitors to mushroom tyrosinase. E195 and H208 are important residues in bacterial tyrosinase, while E230, S245, N249, H252, V262, and S265 bind to inhibitors and are important in forming pi interaction in human tyrosinase.

Quantum chemical dynamics in two dimensions

1993 ◽  
Vol 170 (3) ◽  
pp. 275-293 ◽  
Author(s):  
V.A. Benderskii ◽  
D.E. Makarov ◽  
P.G. Grinevich
Keyword(s):  
Quantum Chemical ◽  
Two Dimensions ◽  
Chemical Dynamics

Mapping Quantum Chemical Dynamics Problems to Spin-Lattice Simulators

2021 ◽  
Author(s):  
Debadrita Saha ◽  
Srinivasan S. Iyengar ◽  
Philip Richerme ◽  
Jeremy M. Smith ◽  
Amr Sabry
Keyword(s):  
Quantum Chemical ◽  
Chemical Dynamics ◽  
Spin Lattice ◽  
Dynamics Problems

scholarly journals Biosynthesis of the microtubule-destabilizing diterpene pseudolaric acid B from golden larch involves an unusual diterpene synthase

2017 ◽  
Vol 114 (5) ◽  
pp. 974-979 ◽  
Author(s):  
Sibongile Mafu ◽  
Prema Sambandaswami Karunanithi ◽  
Teresa Ann Palazzo ◽  
Bronwyn Lee Harrod ◽  
Selina Marakana Rodriguez ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Quantum Chemical ◽  
Site Directed Mutagenesis ◽  
Terpene Synthase ◽  
Proof Of Concept ◽  
Terpene Biosynthesis ◽  
Quantum Chemical Analysis ◽  
Pseudolaric Acid B ◽  
Mechanistic Analysis ◽  
Diterpene Synthase

The diversity of small molecules formed via plant diterpene metabolism offers a rich source of known and potentially new biopharmaceuticals. Among these, the microtubule-destabilizing activity of pseudolaric acid B (PAB) holds promise for new anticancer agents. PAB is found, perhaps uniquely, in the coniferous tree golden larch (Pseudolarix amabilis, Pxa). Here we describe the discovery and mechanistic analysis of golden larch terpene synthase 8 (PxaTPS8), an unusual diterpene synthase (diTPS) that catalyzes the first committed step in PAB biosynthesis. Mining of the golden larch root transcriptome revealed a large TPS family, including the monofunctional class I diTPS PxaTPS8, which converts geranylgeranyl diphosphate into a previously unknown 5,7-fused bicyclic diterpene, coined “pseudolaratriene.” Combined NMR and quantum chemical analysis verified the structure of pseudolaratriene, and co-occurrence with PxaTPS8 and PAB inP.amabilistissues supports the intermediacy of pseudolaratriene in PAB metabolism. Although PxaTPS8 adopts the typical three-domain structure of diTPSs, sequence phylogeny places the enzyme with two-domain TPSs of mono- and sesqui-terpene biosynthesis. Site-directed mutagenesis of PxaTPS8 revealed several catalytic residues that, together with quantum chemical calculations, suggested a substantial divergence of PxaTPS8 from other TPSs leading to a distinct carbocation-driven reaction mechanism en route to the 5,7-trans-fused bicyclic pseudolaratriene scaffold. PxaTPS8 expression in microbial and plant hosts provided proof of concept for metabolic engineering of pseudolaratriene.

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