FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2003808743> ?p ?o ?g. }

• W2003808743 endingPage "783" @default.
• W2003808743 startingPage "775" @default.
• W2003808743 abstract "In drug discovery process, improvement of ADME/Tox properties of lead compounds including metabolic stability is critically important. Cytochrome P450 (CYP) is one of the major metabolizing enzymes and the prediction of sites of metabolism (SOM) on the given lead compounds is key information to modify the compounds to be more stable against metabolism. There are two factors essentially important in SOM prediction. First is accessibility of each substrate atom to the oxygenated Fe atom of heme in a CYP protein, and the other is the oxidative reactivity of each substrate atom. To predict accessibility of substrate atoms to the heme iron, conventional protein-rigid docking simulations have been applied. However, the docking simulations without consideration of protein flexibility often lead to incorrect answers in the case of very flexible proteins such as CYP3A4. In this study, we demonstrated an approach utilizing molecular dynamics (MD) simulation for SOM prediction in which multiple MD runs were executed using different initial structures. We applied this strategy to CYP3A4 and carbamazepine (CBZ) complex. Through 10 ns MD simulations started from five different CYP3A4-CBZ complex models, our approach correctly predicted SOM observed in experiments. The experimentally known epoxidized sites of CBZ by CYP3A4 were successfully predicted as the most accessible sites to the heme iron that was judged from a numerical analysis of calculated ΔGbinding and the frequency of appearance. In contrast, the predictions using protein-rigid docking methods hardly provided the correct SOM due to protein flexibility or inaccuracy of the scoring functions. Our strategy using MD simulation with multiple initial structures will be one of the reliable methods for SOM prediction." @default.
• W2003808743 created "2016-06-24" @default.
• W2003808743 creator A5028458481 @default.
• W2003808743 creator A5035777497 @default.
• W2003808743 creator A5054336320 @default.
• W2003808743 creator A5061258590 @default.
• W2003808743 date "2012-01-01" @default.
• W2003808743 modified "2023-10-16" @default.
• W2003808743 title "Prediction of sites of metabolism in a substrate molecule, instanced by carbamazepine oxidation by CYP3A4" @default.
• W2003808743 cites W1247495390 @default.
• W2003808743 cites W1520746198 @default.
• W2003808743 cites W1563896178 @default.
• W2003808743 cites W1898420966 @default.
• W2003808743 cites W1971252956 @default.
• W2003808743 cites W1973191530 @default.
• W2003808743 cites W1974238774 @default.
• W2003808743 cites W1975206909 @default.
• W2003808743 cites W1976499671 @default.
• W2003808743 cites W1980128327 @default.
• W2003808743 cites W1981747417 @default.
• W2003808743 cites W1985588649 @default.
• W2003808743 cites W1986743541 @default.
• W2003808743 cites W1989814214 @default.
• W2003808743 cites W1992581513 @default.
• W2003808743 cites W1993047099 @default.
• W2003808743 cites W1999848286 @default.
• W2003808743 cites W2002474280 @default.
• W2003808743 cites W2004425718 @default.
• W2003808743 cites W2006358281 @default.
• W2003808743 cites W2014843937 @default.
• W2003808743 cites W2014919794 @default.
• W2003808743 cites W2015661700 @default.
• W2003808743 cites W2019686608 @default.
• W2003808743 cites W2020330990 @default.
• W2003808743 cites W2022867019 @default.
• W2003808743 cites W2024913341 @default.
• W2003808743 cites W2025753091 @default.
• W2003808743 cites W2026544535 @default.
• W2003808743 cites W2027549508 @default.
• W2003808743 cites W2030980866 @default.
• W2003808743 cites W2032864693 @default.
• W2003808743 cites W2035091931 @default.
• W2003808743 cites W2039353947 @default.
• W2003808743 cites W2045327264 @default.
• W2003808743 cites W2047186810 @default.
• W2003808743 cites W2047860814 @default.
• W2003808743 cites W2048214699 @default.
• W2003808743 cites W2049480378 @default.
• W2003808743 cites W2049812048 @default.
• W2003808743 cites W2050456292 @default.
• W2003808743 cites W2051639214 @default.
• W2003808743 cites W2052006868 @default.
• W2003808743 cites W2057802344 @default.
• W2003808743 cites W2059293500 @default.
• W2003808743 cites W2068813094 @default.
• W2003808743 cites W2069123478 @default.
• W2003808743 cites W2073114139 @default.
• W2003808743 cites W2074634520 @default.
• W2003808743 cites W2088604903 @default.
• W2003808743 cites W2088606995 @default.
• W2003808743 cites W2090402650 @default.
• W2003808743 cites W2099826583 @default.
• W2003808743 cites W2106140689 @default.
• W2003808743 cites W2109448546 @default.
• W2003808743 cites W2112764656 @default.
• W2003808743 cites W2117131053 @default.
• W2003808743 cites W2127059331 @default.
• W2003808743 cites W2127290087 @default.
• W2003808743 cites W2127294029 @default.
• W2003808743 cites W2130983257 @default.
• W2003808743 cites W2133017719 @default.
• W2003808743 cites W2136275918 @default.
• W2003808743 cites W2144860443 @default.
• W2003808743 cites W2145621051 @default.
• W2003808743 cites W2149263899 @default.
• W2003808743 cites W2150928826 @default.
• W2003808743 cites W2156423252 @default.
• W2003808743 cites W2164273714 @default.
• W2003808743 cites W2166960145 @default.
• W2003808743 cites W2170439793 @default.
• W2003808743 cites W2395483284 @default.
• W2003808743 cites W8127528 @default.
• W2003808743 doi "https://doi.org/10.1016/j.bmc.2011.12.004" @default.
• W2003808743 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22197672" @default.
• W2003808743 hasPublicationYear "2012" @default.
• W2003808743 type Work @default.
• W2003808743 sameAs 2003808743 @default.
• W2003808743 citedByCount "36" @default.
• W2003808743 countsByYear W20038087432012 @default.
• W2003808743 countsByYear W20038087432013 @default.
• W2003808743 countsByYear W20038087432014 @default.
• W2003808743 countsByYear W20038087432015 @default.
• W2003808743 countsByYear W20038087432016 @default.
• W2003808743 countsByYear W20038087432017 @default.
• W2003808743 countsByYear W20038087432018 @default.
• W2003808743 countsByYear W20038087432019 @default.
• W2003808743 countsByYear W20038087432020 @default.
• W2003808743 countsByYear W20038087432021 @default.

• next