Journal
BIOINFORMATICS
Volume 24, Issue 16, Pages I207-I212Publisher
OXFORD UNIV PRESS
DOI: 10.1093/bioinformatics/btn268
Keywords
-
Categories
Funding
- NLM NIH HHS [R01 LM007329, R01-LM07329-01, R01 LM007329-06] Funding Source: Medline
Ask authors/readers for more resources
Motivation: Mutating residues into alanine (alanine scanning) is one of the fastest experimental means of probing hypotheses about protein function. Alanine scans can reveal functional hot spots, i.e. residues that alter function upon mutation. In vitro mutagenesis is cumbersome and costly: probing all residues in a protein is typically as impossible as substituting by all non-native amino acids. In contrast, such exhaustive mutagenesis is feasible in silico. Results: Previously, we developed SNAP to predict functional changes due to non-synonymous single nucleotide polymorphisms. Here, we applied SNAP to all experimental mutations in the ASEdb database of alanine scans; we identi.ed 70 of the hot spots (1 kCal/mol change in binding energy); more severe changes were predicted more accurately. Encouraged, we carried out a complete all-against-all in silico mutagenesis for human glucokinase. Many of the residues predicted as functionally important have indeed been con.rmed in the literature, others await experimental veri.cation, and our method is ready to aid in the design of in vitro mutagenesis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available