Using Structural Biology to Support Variant Assessment - Webinar - Ambry Genetics

Explore the application of structural biology in genetic variant assessment through this informative webinar presented by Ambry Genetics. Gain insights into leveraging biophysical principles to evaluate the functional impact of genetic variants, complementing traditional assessment methods. Learn about general biophysical approaches and their practical applications in determining variant deleteriousness. Discover how structural evidence can be combined with other categories of evidence to reassess variants of unknown significance. Delve into topics such as ACMG guidelines, protein structure and function, amino acids, sequence alignments, conservation, and molecular interactions. Understand the four levels of protein structure and how they relate to variant assessment. Examine case studies, including the analysis of BRCA2 p.D2723N, to see structural biology principles in action. Benefit from the expertise of Dr. Adam Chamberlin, Principal Structural Biologist at Ambry Genetics, as he shares his extensive knowledge in quantum and physical chemistry, structural biology, and mathematical modeling.

Intro
ACMG Guidelines General variant classification guideline
Structural Data Number of structures available
Available Lines of Evidence What can we use to assess variants?
Protein Structure Defines the Function What is the central dogma of molecular biology?
Information Levels DNA, RNA, and protein
Amino Acids The basic building blocks
Sequence Alignments & Conservation Additional data for variant assessment
Protein Structure Four levels of protein structure
Structural Biology & 3D Protein Structure Accounting for folding
Biophysical Method Overview Using classical mechanics to represent proteins
Molecular Interactions Functional disruption through lost interactions
Structural Biology in Variant Assessment Possible outcomes
Predicted Stability Changes Comparing energies
Structural Motif Disruption Structural details of motif assessment
Biomolecular Interactions Arginine finger interacts with the DNA
BRCA2 p.D2723N Destabilizing structure
Structural Biology Applications Tools in the toolbox Dynamics
Acknowledgements Thank you for your contributions, insight, and help