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P3‐081: POST‐VARIANT CALLING QUALITY CONTROL (QC) PIPELINE AND MULTI‐PIPELINE GENOTYPE CONSENSUS CALLER FOR LARGE‐SCALE WHOLE GENOME AND WHOLE EXOME SEQUENCING STUDIES
Author(s) -
Malamon John Stephen,
Naj Adam C.
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.1437
Subject(s) - indel , exome sequencing , whole genome sequencing , pipeline (software) , exome , computer science , data mining , genome , computational biology , genetics , genotype , biology , single nucleotide polymorphism , gene , mutation , programming language
Background: Neuromyelitis Optica Spectrum Disorders(NMOSD) is a multiple sclerosis-like immunopathology diseases affecting optic nerves and the depostion of a typical immunoglobulin, called NMO-IgG, against the water channel Aquaporin-4(AQP4). Preventing NMO-IgG binfing would represent a valuable molecular strategy for a focusrd NMOSD therapy. Methods: In this study, we focused on the designing of AQP4 inhibitors, the dynamic analysis of the key amino acid mutants was carried out by using the method of molecular dynamics(MD), analyzed the crystal structure data of AQP4 on RCSB, the key regions of active centers were studied. Then structure-based design were employed to design novel AQP4 inhibitors using the National Super Computing Platform, have screened more than 350000 compounds. Results: The amino acid mutation located in the loop C area did not cause its conformational change, but across the extracellular cyclic structure affected loop A. The mutation of threonine could completely reverse the movement tendency of loop A. The main reason for this phenomenon is that the interaction force between the residues in the loop A and the hydrogen bond between loop A and loop C. Mutation of T137 and P138, although beneficial to the prevention and treatment of NMOSD, but it will affect the choice of permeability. From the screening results, showingmany of double-Steroidal Bioconjugates and dense conjugated heterocyclic as lead compounds. Conclusions: The antibody response to AQP4 antigen is an important diagnostic criterion for the NMOSD, but it’s also a key therapeutic target. Based on the analysis of the crystal structure of the receptor, the results show that AQP4 has good drug target characteristics. As a target, the selected compounds are not only suitable for the study of NMOSD, but also for other diseases that are associated with aquaporins.