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10.1186/s13321-017-0202-6 http://scihub22266oqcxt.onion/10.1186/s13321-017-0202-6 C5337232!5337232!28303164     free     free     free Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Cheminform 2017 ; 9 (ä): ä Nephropedia Template TP {{tp|p=28303164|t=2017. Adverse drug reactions triggered by the common HLA-B*57:01 variant: a molecular docking study |pdf=|usr=}}{{28303164}} gab.com Text Adverse drug reactions triggered by the common HLA-B*57:01 variant: a molecular docking study JO: J Cheminform http://www.kidney.de/pget.php?&tw=1&pmid=28303164 #FOAvip Background: Human leukocyte antigen (HLA) surface proteins are directly involved in idiosyncratic adverse drug reactions. Herein, we present a structure-based analysis of the common HLA-B*57:01 variant known to be responsible for several HLA-linked adverse effects such as the abacavir hypersensitivity syndrome. Methods: First, we analyzed three X-ray crystal structures involving the HLA-B*57:01 protein variant, the anti-HIV drug abacavir, and different co-binding peptides present in the antigen-binding cleft. We superimposed the three complexes and showed that abacavir had no significant conformational variation whatever the co-binding peptide. Second, we self-docked abacavir in the HLA-B*57:01 antigen binding cleft with and without peptide using Glide. Third, we docked a small test set of 13 drugs with known ADRs and suspected HLA associations. Results: In the presence of an endogenous co-binding peptide, we found a significant stabilization (~2 kcal/mol) of the docking scores and identified several modified abacavir?peptide interactions indicating that the peptide does play a role in stabilizing the HLA?abacavir complex. Next, our model was used to dock a test set of 13 drugs at HLA-B*57:01 and measured their predicted binding affinities. Drug-specific interactions were observed at the antigen-binding cleft and we were able to discriminate the compounds with known HLA-B*57:01 liability from inactives. Conclusions: Overall, our study highlights the relevance of molecular docking for evaluating and analyzing complex HLA?drug interactions. This is particularly important for virtual drug screening over thousands of HLA variants as other experimental techniques (e.g., in vitro HTS) and computational approaches (e.g., molecular dynamics) are more time consuming and expensive to conduct. As the attention for drugs? HLA liability is on the rise, we believe this work participates in encouraging the use of molecular modeling for reliably studying and predicting HLA?drug interactions. Graphical abstract. Electronic supplementary material: The online version of this article (doi:10.1186/s13321-017-0202-6) contains supplementary material, which is available to authorized users. Twit Text FOAVip Adverse drug reactions triggered by the common HLA-B*57:01 variant: a molecular docking study ????J Cheminform http://www.kidney.de/pget.php?&tw=1&pmid=28303164 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28303164 #FOAvip English Wikipedia <ref>{{Cite pmid|28303164}}</ref> Adverse drug reactions triggered by the common HLA-B*57:01 variant: a molecular docking study #MMPMID28303164 Van Den Driessche G; Fourches D J Cheminform 2017[]; 9 (ä): ä PMID28303164show ga Background: Human leukocyte antigen (HLA) surface proteins are directly involved in idiosyncratic adverse drug reactions. Herein, we present a structure-based analysis of the common HLA-B*57:01 variant known to be responsible for several HLA-linked adverse effects such as the abacavir hypersensitivity syndrome. Methods: First, we analyzed three X-ray crystal structures involving the HLA-B*57:01 protein variant, the anti-HIV drug abacavir, and different co-binding peptides present in the antigen-binding cleft. We superimposed the three complexes and showed that abacavir had no significant conformational variation whatever the co-binding peptide. Second, we self-docked abacavir in the HLA-B*57:01 antigen binding cleft with and without peptide using Glide. Third, we docked a small test set of 13 drugs with known ADRs and suspected HLA associations. Results: In the presence of an endogenous co-binding peptide, we found a significant stabilization (~2 kcal/mol) of the docking scores and identified several modified abacavir?peptide interactions indicating that the peptide does play a role in stabilizing the HLA?abacavir complex. Next, our model was used to dock a test set of 13 drugs at HLA-B*57:01 and measured their predicted binding affinities. Drug-specific interactions were observed at the antigen-binding cleft and we were able to discriminate the compounds with known HLA-B*57:01 liability from inactives. Conclusions: Overall, our study highlights the relevance of molecular docking for evaluating and analyzing complex HLA?drug interactions. This is particularly important for virtual drug screening over thousands of HLA variants as other experimental techniques (e.g., in vitro HTS) and computational approaches (e.g., molecular dynamics) are more time consuming and expensive to conduct. As the attention for drugs? HLA liability is on the rise, we believe this work participates in encouraging the use of molecular modeling for reliably studying and predicting HLA?drug interactions. Graphical abstract. Electronic supplementary material: The online version of this article (doi:10.1186/s13321-017-0202-6) contains supplementary material, which is available to authorized users. äAdverse drug reactions triggered by the common HLA-B*57:01 variant: a (epmc).pdf DeepDyve Pubget Overpricing