Using Energy-Minimization Profiles to Measure Protein Resistance to Drugs

التفاصيل البيبلوغرافية
العنوان: Using Energy-Minimization Profiles to Measure Protein Resistance to Drugs
المؤلفون: Edward Thompson, Ryan Rapoport, Filip Jagodzinski, Tess Thackray, Cecilia Kalthoff
المصدر: Proceedings of the 11th ACM International Conference on Bioinformatics, Computational Biology and Health Informatics.
بيانات النشر: ACM, 2020.
سنة النشر: 2020
مصطلحات موضوعية: chemistry.chemical_classification, 0303 health sciences, Mutation, 030306 microbiology, Chemistry, In silico, Point mutation, 0206 medical engineering, Mutant, Mutagenesis (molecular biology technique), 02 engineering and technology, Computational biology, Ligand (biochemistry), medicine.disease_cause, Amino acid, 03 medical and health sciences, medicine, Peptide sequence, 020602 bioinformatics
الوصف: A mutation to the amino acid sequence of a protein can cause a biomolecule to be resistant to the intended effects of a drug. Assessing the changes of a drug's efficacy in response to mutations via mutagenesis wet-lab experiments is prohibitively time consuming for even a single point mutation, let alone for all possible mutations. Existing approaches for inferring mutation-induced drug resistance are available, but all of them reason about mutations of residues at or very near the protein-drug interface. However, there are examples of mutations far away from the region where the ligand binds, but which nonetheless render a protein resistant to the effects of the drug. We present a proof-of-concept computational pipeline that generates in silico the set of all possible single point mutations in a protein-ligand complex. We assess drug resistance via energy profiles for short runs of molecular dynamics of the mutants. We assess the impact of mutations far away from the protein-drug interface and provide case studies for exploring how amino acid substitutions both near and far away from where the ligand interacts with a protein target have a stabilizing or destabilizing effect on the protein-drug complex.
DOI: 10.1145/3388440.3414703
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::afe743219bc9de6ff600f755f5e3f99d
https://doi.org/10.1145/3388440.3414703
رقم الانضمام: edsair.doi...........afe743219bc9de6ff600f755f5e3f99d
قاعدة البيانات: OpenAIRE