Matches in SemOpenAlex for { <https://semopenalex.org/work/W2953485655> ?p ?o ?g. }
- W2953485655 endingPage "3213" @default.
- W2953485655 startingPage "3198" @default.
- W2953485655 abstract "Assessment of permeability is a critical step in the drug development process for selection of drug candidates with favorable ADME properties. We have developed a novel physics-based method for fast computational modeling of passive permeation of diverse classes of molecules across lipid membranes. The method is based on heterogeneous solubility-diffusion theory and operates with all-atom 3D structures of solutes and the anisotropic solvent model of the lipid bilayer characterized by transbilayer profiles of dielectric and hydrogen bonding capacity parameters. The optimal translocation pathway of a solute is determined by moving an ensemble of representative conformations of the molecule through the dioleoyl-phosphatidylcholine (DOPC) bilayer and optimizing their rotational orientations in every point of the transmembrane trajectory. The method calculates (1) the membrane-bound state of the solute molecule; (2) free energy profile of the solute along the permeation pathway; and (3) the permeability coefficient obtained by integration over the transbilayer energy profile and assuming a constant size-dependent diffusivity along the membrane normal. The accuracy of the predictions was evaluated against experimental permeability coefficients measured in pure lipid membranes (for 78 compounds, R2 was 0.88 and rmse was 1.15 log units), PAMPA-DS (for 280 compounds, R2 was 0.75 and rmse was 1.59 log units), BBB (for 182 compounds, R2 was 0.69 and rmse was 0.87 log units), and Caco-2/MDCK assays (for 165 compounds, R2 was 0.52 and rmse was 0.89 log units)." @default.
- W2953485655 created "2019-07-12" @default.
- W2953485655 creator A5006189599 @default.
- W2953485655 creator A5056114039 @default.
- W2953485655 date "2019-07-01" @default.
- W2953485655 modified "2023-10-17" @default.
- W2953485655 title "Physics-Based Method for Modeling Passive Membrane Permeability and Translocation Pathways of Bioactive Molecules" @default.
- W2953485655 cites W1577254788 @default.
- W2953485655 cites W1580839473 @default.
- W2953485655 cites W1594001267 @default.
- W2953485655 cites W1679872389 @default.
- W2953485655 cites W1764028344 @default.
- W2953485655 cites W1917632116 @default.
- W2953485655 cites W1971209681 @default.
- W2953485655 cites W1971212169 @default.
- W2953485655 cites W1971578904 @default.
- W2953485655 cites W1979732884 @default.
- W2953485655 cites W1981598707 @default.
- W2953485655 cites W1986688691 @default.
- W2953485655 cites W1988678866 @default.
- W2953485655 cites W1989396696 @default.
- W2953485655 cites W1992578799 @default.
- W2953485655 cites W1995336204 @default.
- W2953485655 cites W1995994436 @default.
- W2953485655 cites W1997381364 @default.
- W2953485655 cites W1999841301 @default.
- W2953485655 cites W2001562217 @default.
- W2953485655 cites W2007070530 @default.
- W2953485655 cites W2007859813 @default.
- W2953485655 cites W2010263368 @default.
- W2953485655 cites W2012556902 @default.
- W2953485655 cites W2022227682 @default.
- W2953485655 cites W2023621385 @default.
- W2953485655 cites W2023750903 @default.
- W2953485655 cites W2024815910 @default.
- W2953485655 cites W2026164878 @default.
- W2953485655 cites W2026467865 @default.
- W2953485655 cites W2029564741 @default.
- W2953485655 cites W2029653438 @default.
- W2953485655 cites W2031576029 @default.
- W2953485655 cites W2033757486 @default.
- W2953485655 cites W2034241231 @default.
- W2953485655 cites W2034549041 @default.
- W2953485655 cites W2034939322 @default.
- W2953485655 cites W2035629195 @default.
- W2953485655 cites W2036547515 @default.
- W2953485655 cites W2040743161 @default.
- W2953485655 cites W2042678771 @default.
- W2953485655 cites W2048599811 @default.
- W2953485655 cites W2054884372 @default.
- W2953485655 cites W2065114648 @default.
- W2953485655 cites W2073762710 @default.
- W2953485655 cites W2077142764 @default.
- W2953485655 cites W2078411900 @default.
- W2953485655 cites W2080946353 @default.
- W2953485655 cites W2082432593 @default.
- W2953485655 cites W2107851883 @default.
- W2953485655 cites W2109312400 @default.
- W2953485655 cites W2109343162 @default.
- W2953485655 cites W2117092343 @default.
- W2953485655 cites W2117676629 @default.
- W2953485655 cites W2121678787 @default.
- W2953485655 cites W2128245586 @default.
- W2953485655 cites W2128444449 @default.
- W2953485655 cites W2134470186 @default.
- W2953485655 cites W2135845551 @default.
- W2953485655 cites W2136359146 @default.
- W2953485655 cites W2142528678 @default.
- W2953485655 cites W2145020089 @default.
- W2953485655 cites W2147796031 @default.
- W2953485655 cites W2156835500 @default.
- W2953485655 cites W2158119082 @default.
- W2953485655 cites W2162235098 @default.
- W2953485655 cites W2169546341 @default.
- W2953485655 cites W2205647194 @default.
- W2953485655 cites W2231559318 @default.
- W2953485655 cites W2262786960 @default.
- W2953485655 cites W2264334467 @default.
- W2953485655 cites W2315489011 @default.
- W2953485655 cites W2315776829 @default.
- W2953485655 cites W2319902168 @default.
- W2953485655 cites W2323907991 @default.
- W2953485655 cites W2324930475 @default.
- W2953485655 cites W2326404322 @default.
- W2953485655 cites W2333894344 @default.
- W2953485655 cites W2338084851 @default.
- W2953485655 cites W2339460745 @default.
- W2953485655 cites W2340673398 @default.
- W2953485655 cites W2345340078 @default.
- W2953485655 cites W2346348293 @default.
- W2953485655 cites W2564974142 @default.
- W2953485655 cites W2585375015 @default.
- W2953485655 cites W2610507014 @default.
- W2953485655 cites W2620998958 @default.
- W2953485655 cites W2803333743 @default.
- W2953485655 cites W2804716008 @default.
- W2953485655 cites W2895662630 @default.
- W2953485655 cites W2895956916 @default.