Matches in SemOpenAlex for { <https://semopenalex.org/work/W3028831932> ?p ?o ?g. }
- W3028831932 endingPage "4684" @default.
- W3028831932 startingPage "4669" @default.
- W3028831932 abstract "Accuracy of protein–ligand binding free energy calculations utilizing implicit solvent models is critically affected by parameters of the underlying dielectric boundary, specifically, the atomic and water probe radii. Here, a global multidimensional optimization pipeline is developed to find optimal atomic radii specifically for protein–ligand binding calculations in implicit solvent. The computational pipeline has these three key components: (1) a massively parallel implementation of a deterministic global optimization algorithm (VTDIRECT95), (2) an accurate yet reasonably fast generalized Born implicit solvent model (GBNSR6), and (3) a novel robustness metric that helps distinguish between nearly degenerate local minima via a postprocessing step of the optimization. A graph-based “kT-connectivity” approach to explore and visualize the multidimensional energy landscape is proposed: local minima that can be reached from the global minimum without exceeding a given energy threshold (kT) are considered to be connected. As an illustration of the capabilities of the optimization pipeline, we apply it to find a global optimum in the space of just five radii: four atomic (O, H, N, and C) radii and water probe radius. The optimized radii, ρW = 1.37 Å, ρC = 1.40 Å, ρH = 1.55 Å, ρN = 2.35 Å, and ρO = 1.28 Å, lead to a closer agreement of electrostatic binding free energies with the explicit solvent reference than two commonly used sets of radii previously optimized for small molecules. At the same time, the ability of the optimizer to find the global optimum reveals fundamental limits of the common two-dielectric implicit solvation model: the computed electrostatic binding free energies are still almost 4 kcal/mol away from the explicit solvent reference. The proposed computational approach opens the possibility to further improve the accuracy of practical computational protocols for binding free energy calculations." @default.
- W3028831932 created "2020-06-05" @default.
- W3028831932 creator A5022075325 @default.
- W3028831932 creator A5068161656 @default.
- W3028831932 creator A5077198069 @default.
- W3028831932 creator A5081213503 @default.
- W3028831932 date "2020-05-25" @default.
- W3028831932 modified "2023-10-10" @default.
- W3028831932 title "Multidimensional Global Optimization and Robustness Analysis in the Context of Protein–Ligand Binding" @default.
- W3028831932 cites W125242125 @default.
- W3028831932 cites W1475098999 @default.
- W3028831932 cites W1553864921 @default.
- W3028831932 cites W178391439 @default.
- W3028831932 cites W1964156173 @default.
- W3028831932 cites W1968755416 @default.
- W3028831932 cites W1969046853 @default.
- W3028831932 cites W1969674470 @default.
- W3028831932 cites W1971317029 @default.
- W3028831932 cites W1972361027 @default.
- W3028831932 cites W1973060079 @default.
- W3028831932 cites W1975081376 @default.
- W3028831932 cites W1976499671 @default.
- W3028831932 cites W1977867181 @default.
- W3028831932 cites W1982062047 @default.
- W3028831932 cites W1984231149 @default.
- W3028831932 cites W1987729396 @default.
- W3028831932 cites W1988576626 @default.
- W3028831932 cites W1996551126 @default.
- W3028831932 cites W1997639796 @default.
- W3028831932 cites W1999938940 @default.
- W3028831932 cites W2000613080 @default.
- W3028831932 cites W2004360551 @default.
- W3028831932 cites W2008015300 @default.
- W3028831932 cites W2008873311 @default.
- W3028831932 cites W2012707864 @default.
- W3028831932 cites W2015863994 @default.
- W3028831932 cites W2020561870 @default.
- W3028831932 cites W2022492426 @default.
- W3028831932 cites W2023592877 @default.
- W3028831932 cites W2024852705 @default.
- W3028831932 cites W2026467865 @default.
- W3028831932 cites W2027407693 @default.
- W3028831932 cites W2029582401 @default.
- W3028831932 cites W2032431601 @default.
- W3028831932 cites W2041834854 @default.
- W3028831932 cites W2047730466 @default.
- W3028831932 cites W2050273205 @default.
- W3028831932 cites W2050774715 @default.
- W3028831932 cites W2055606802 @default.
- W3028831932 cites W2056787579 @default.
- W3028831932 cites W2058653824 @default.
- W3028831932 cites W2066455419 @default.
- W3028831932 cites W2067451625 @default.
- W3028831932 cites W2067845685 @default.
- W3028831932 cites W2068465600 @default.
- W3028831932 cites W2073146967 @default.
- W3028831932 cites W2073662804 @default.
- W3028831932 cites W2075369230 @default.
- W3028831932 cites W2075662564 @default.
- W3028831932 cites W2082259277 @default.
- W3028831932 cites W2084550263 @default.
- W3028831932 cites W2087315981 @default.
- W3028831932 cites W2091574192 @default.
- W3028831932 cites W2095460759 @default.
- W3028831932 cites W2103860533 @default.
- W3028831932 cites W2103945336 @default.
- W3028831932 cites W2110562802 @default.
- W3028831932 cites W2110670340 @default.
- W3028831932 cites W2112610155 @default.
- W3028831932 cites W2113741278 @default.
- W3028831932 cites W2116903488 @default.
- W3028831932 cites W2123489408 @default.
- W3028831932 cites W2127116852 @default.
- W3028831932 cites W2141795095 @default.
- W3028831932 cites W2144775933 @default.
- W3028831932 cites W2147993766 @default.
- W3028831932 cites W2164270482 @default.
- W3028831932 cites W2170802700 @default.
- W3028831932 cites W2171891719 @default.
- W3028831932 cites W2259935178 @default.
- W3028831932 cites W2313543200 @default.
- W3028831932 cites W2316175136 @default.
- W3028831932 cites W2324363054 @default.
- W3028831932 cites W2327525605 @default.
- W3028831932 cites W2329540625 @default.
- W3028831932 cites W2330055113 @default.
- W3028831932 cites W2332712348 @default.
- W3028831932 cites W2485959410 @default.
- W3028831932 cites W2564199680 @default.
- W3028831932 cites W2742305903 @default.
- W3028831932 cites W2768709305 @default.
- W3028831932 cites W2783855936 @default.
- W3028831932 cites W2785772798 @default.
- W3028831932 cites W2790013445 @default.
- W3028831932 cites W2805498355 @default.
- W3028831932 cites W2922133186 @default.
- W3028831932 cites W2942075139 @default.
- W3028831932 cites W2951039542 @default.