Abstract
The Mutation-Minimization Method (MuMi) to study the local response of proteins to point mutations has been introduced here. The heat shock protein Hsp70 as the test system since it displays features that have been studied in great detail has been used here. It has many conserved residues, serves several different functions on each of its domains, and displays interdomain allostery. For the analysis of spatial arrangement of residues within the protein, the network properties of the wild type (WT) protein as well as its all single alanine residue mutants using MuMi has been investigated. The measures to express the amount of change from the WT structure upon mutation and compare these deviations to find potential critical sites have been proposed. The functional significance of the potential sites to the parameter that uncovers them has been mapped. It was found that sites directly involved in binding were sensitive to mutations and were characterized by large displacements. On the other hand, sites that steer large conformational changes typically had increased reachability upon alanine mutations occurring elsewhere in the protein. Finally, residues that control communication within and between domains reside on the largest number of paths connecting pairs of residues in the protein.
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
