title: Impact of genetic variation on three dimensional structure and function of proteins.
abstract: The Protein Data Bank (PDB; http://wwpdb.org) was established in 1971 as the first open access digital data resource in biology with seven protein structures as its initial holdings. The global PDB archive now contains more than 126,000 experimentally determined atomic level three-dimensional (3D) structures of biological macromolecules (proteins, DNA, RNA), all of which are freely accessible via the Internet. Knowledge of the 3D structure of the gene product can help in understanding its function and role in disease. Of particular interest in the PDB archive are proteins for which 3D structures of genetic variant proteins have been determined, thus revealing atomic-level structural differences caused by the variation at the DNA level. Herein, we present a systematic and qualitative analysis of such cases. We observe a wide range of structural and functional changes caused by single amino acid differences, including changes in enzyme activity, aggregation propensity, structural stability, binding, and dissociation, some in the context of large assemblies. Structural comparison of wild type and mutated proteins, when both are available, provide insights into atomic-level structural differences caused by the genetic variation.
authors.affiliation: Bioinformatics and Medical Informatics, San Diego State University, San Diego, California, United States of America.
authors.forename: Roshni
authors.initials: R
authors.lastname: Bhattacharya
authors.affiliation: RCSB Protein Data Bank, San Diego Supercomputer Center, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Rose
authors.affiliation: RCSB Protein Data Bank, San Diego Supercomputer Center, University of California San Diego, La Jolla, California, United States of America.|RCSB Protein Data Bank, Department of Chemistry and Chemical Biology, Center for Integrative Proteomics Research, Institute for Quantitative Biomedicine, and Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, Piscataway, New Jersey, United States of America.|Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Burley
authors.affiliation: RCSB Protein Data Bank, San Diego Supercomputer Center, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Andreas
authors.identifier: http://orcid.org/0000-0001-6346-6391
authors.initials: A
authors.lastname: Prlić
mesh_terms: D059472:Exome; D014644:Genetic Variation; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000737:chemistry* / Q000502:physiology*; D013329:Structure-Activity Relationship
chemical_list: D011506:Proteins