Analysing the ability to retain sidechain hydrogen-bonds in mutant proteins.
BACKGROUND
Hydrogen bonds are one of the most important inter-atomic interactions in biology. Previous experimental, theoretical and bioinformatics analyses have shown that the hydrogen bonding potential of amino acids is generally satisfied and that buried unsatisfied hydrogen-bond-capable residues are destabilizing. When studying mutant proteins, or introducing mutations to residues involved in hydrogen bonding, one needs to know whether a hydrogen bond can be maintained. Our aim, therefore, was to develop a rapid method to evaluate whether a sidechain can form a hydrogen-bond.


RESULTS
A novel knowledge-based approach was developed in which the conformations accessible to the residues involved are taken into account. Residues involved in hydrogen bonds in a set of high resolution crystal structures were analyzed and this analysis is then applied to a given protein. The program was applied to assess mutations in the tumour-suppressor protein, p53. This raised the number of distinct mutations identified as disrupting sidechain-sidechain hydrogen bonding from 181 in our previous analysis to 202 in this analysis.
Cuff
Alison L
AL
School of Animal and Microbial Sciences, University of Reading Whiteknights, PO Box 228, Reading RG6 6AJ, UK.
Janes
Robert W
RW
Martin
Andrew C R
AC
D000465:Algorithms; D000818:Animals; D001216:Asparagine / Q000737:chemistry; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry*; D009154:Mutation; D009584:Nitrogen / Q000737:chemistry; D012984:Software; D013816:Thermodynamics; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry; D014443:Tyrosine / Q000737:chemistry
D050505:Mutant Proteins; D016159:Tumor Suppressor Protein p53; D014443:Tyrosine; D001216:Asparagine; D009584:Nitrogen