Jump to main content
Jump to site search
SCHEDULED MAINTENANCE Close the message box

Maintenance work is planned for Monday 16 August 2021 from 07:00 to 23:59 (BST).

Website performance may be temporarily affected and you may not be able to access some PDFs or images. If this does happen, refreshing your web browser should resolve the issue. We apologise for any inconvenience this might cause and thank you for your patience.


Issue 28, 2016

The role of side chain entropy and mutual information for improving the de novo design of Kemp eliminases KE07 and KE70

Author affiliations

Abstract

Side chain entropy and mutual entropy information between residue pairs have been calculated for two de novo designed Kemp eliminase enzymes, KE07 and KE70, and for their most improved versions at the end of laboratory directed evolution (LDE). We find that entropy, not just enthalpy, helped to destabilize the preference for the reactant state complex of the designed enzyme as well as favoring stabilization of the transition state complex for the best LDE enzymes. Furthermore, residues with the highest side chain couplings as measured by mutual information, when experimentally mutated, were found to diminish or annihilate catalytic activity, some of which were far from the active site. In summary, our findings demonstrate how side chain fluctuations and their coupling can be an important design feature for de novo enzymes, and furthermore could be utilized in the computational steps in lieu of or in addition to the LDE steps in future enzyme design projects.

Graphical abstract: The role of side chain entropy and mutual information for improving the de novo design of Kemp eliminases KE07 and KE70

Supplementary files

Article information


Submitted
26 May 2016
Accepted
20 Jun 2016
First published
24 Jun 2016

Phys. Chem. Chem. Phys., 2016,18, 19386-19396
Article type
Paper

The role of side chain entropy and mutual information for improving the de novo design of Kemp eliminases KE07 and KE70

A. Bhowmick, S. C. Sharma, H. Honma and T. Head-Gordon, Phys. Chem. Chem. Phys., 2016, 18, 19386 DOI: 10.1039/C6CP03622H

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.


Social activity

Search articles by author

Spotlight

Advertisements