排序方式: 共有95条查询结果,搜索用时 218 毫秒
91.
Vytautas Gapsys Laura Prez-Benito Matteo Aldeghi Daniel Seeliger Herman van Vlijmen Gary Tresadern Bert L. de Groot 《Chemical science》2020,11(4):1140
Ligand binding affinity calculations based on molecular dynamics (MD) simulations and non-physical (alchemical) thermodynamic cycles have shown great promise for structure-based drug design. However, their broad uptake and impact is held back by the notoriously complex setup of the calculations. Only a few tools other than the free energy perturbation approach by Schrödinger Inc. (referred to as FEP+) currently enable end-to-end application. Here, we present for the first time an approach based on the open-source software pmx that allows to easily set up and run alchemical calculations for diverse sets of small molecules using the GROMACS MD engine. The method relies on theoretically rigorous non-equilibrium thermodynamic integration (TI) foundations, and its flexibility allows calculations with multiple force fields. In this study, results from the Amber and Charmm force fields were combined to yield a consensus outcome performing on par with the commercial FEP+ approach. A large dataset of 482 perturbations from 13 different protein–ligand datasets led to an average unsigned error (AUE) of 3.64 ± 0.14 kJ mol−1, equivalent to Schrödinger''s FEP+ AUE of 3.66 ± 0.14 kJ mol−1. For the first time, a setup is presented for overall high precision and high accuracy relative protein–ligand alchemical free energy calculations based on open-source software.Relative ligand binding affinity calculations based on molecular dynamics (MD) simulations and non-physical (alchemical) thermodynamic cycles have shown great promise for structure-based drug design. 相似文献
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93.
V. Getautis M. Daskevicene A. Stanisauskaite 《Chemistry of Heterocyclic Compounds》2000,36(7):787-791
The reactions of 9-(2,3-epoxypropyl)carbazole and the glycidyl ether of 1,3-di(9-carbazolyl)-2-propanol with 2-phenylindole were studied. The addition of the epoxypropylcarbazole derivatives to 2-phenylindole in 2-butanone in the presence of alkali at room temperature occurs at the nitrogen atom, while the addition proceeds at C(3) upon heating these epoxy compounds with 2-phenylindole.Kaunas Technological University, Kaunas LT-3028, Lithuania. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 898–902, July, 2000. 相似文献
94.
Smirnovas V Winter R Funck T Dzwolak W 《The journal of physical chemistry. B》2005,109(41):19043-19045
In this work, we performed a detailed thermodynamic study of an aggregation-prone polypeptide, polylysine, to gain a deeper insight into the scenario of physicochemical events during its unfolding, aggregation, and amyloidogenesis. The precise and simultaneous determination of the partial molar volume, the heat capacity, and the coefficients of thermal expansion, as well as adiabatic and isothermal compressibility of the protein upon unfolding and aggregation, yields a thermodynamic picture of the aggregation process highlighting the importance of volume fluctuations during unfolding and amyloidogenesis of proteins. 相似文献
95.
Vytautas Gapsys Bert L. de Groot Rodolfo Briones 《Journal of computer-aided molecular design》2013,27(10):845-858
In the field of biomolecular simulations, dynamics of phospholipid membranes is of special interest. A number of proteins, including channels, transporters, receptors and short peptides are embedded in lipid bilayers and tightly interact with phospholipids. While the experimental measurements report on the spatial and/or temporal average membrane properties, simulation results are not restricted to the average properties. In the current study, we present a collection of methods for an efficient local membrane property calculation, comprising bilayer thickness, area per lipid, deuterium order parameters, Gaussian and mean curvature. The local membrane property calculation allows for a direct mapping of the membrane features, which subsequently can be used for further analysis and visualization of the processes of interest. The main features of the described methods are highlighted in a number of membrane systems, namely: a pure dimyristoyl-phosphatidyl-choline (DMPC) bilayer, a fusion peptide interacting with a membrane, voltage-dependent anion channel protein embedded in a DMPC bilayer, cholesterol enriched bilayer and a coarse grained simulation of a curved palmitoyl-oleoyl-phosphatidyl-choline lipid membrane. The local membrane property analysis proves to provide an intuitive and detailed view on the observables that are otherwise interpreted as averaged bilayer properties. 相似文献