Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Modeling catalytic promiscuity in the alkaline phosphatase superfamily
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology. (Kamerlin)
2013 (English)In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 15, no 27, 11160-11177 p.Article in journal (Refereed) Published
Abstract [en]

In recent years, it has become increasingly clear that promiscuity plays a key role in the evolution of new enzyme function. This finding has helped to elucidate fundamental aspects of molecular evolution. While there has been extensive experimental work on enzyme promiscuity, computational modeling of the chemical details of such promiscuity has traditionally fallen behind the advances in experimental studies, not least due to the nearly prohibitive computational cost involved in examining multiple substrates with multiple potential mechanisms and binding modes in atomic detail with a reasonable degree of accuracy. However, recent advances in both computational methodologies and power have allowed us to reach a stage in the field where we can start to overcome this problem, and molecular simulations can now provide accurate and efficient descriptions of complex biological systems with substantially less computational cost. This has led to significant advances in our understanding of enzyme function and evolution in a broader sense. Here, we will discuss currently available computational approaches that can allow us to probe the underlying molecular basis for enzyme specificity and selectivity, discussing the inherent strengths and weaknesses of each approach. As a case study, we will discuss recent computational work on different members of the alkaline phosphatase superfamily (AP) using a range of different approaches, showing the complementary insights they have provided. We have selected this particular superfamily, as it poses a number of significant challenges for theory, ranging from the complexity of the actual reaction mechanisms involved to the reliable modeling of the catalytic metal centers, as well as the very large system sizes. We will demonstrate that, through current advances in methodologies, computational tools can provide significant insight into the molecular basis for catalytic promiscuity, and, therefore, in turn, the mechanisms of protein functional evolution.

Place, publisher, year, edition, pages
2013. Vol. 15, no 27, 11160-11177 p.
National Category
Theoretical Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-202285DOI: 10.1039/C3CP51179KISI: 000320557600001OAI: oai:DiVA.org:uu-202285DiVA: diva2:631681
Funder
EU, European Research Council, 306474Swedish Research Council, 2010-5026
Available from: 2013-06-22 Created: 2013-06-22 Last updated: 2017-12-06Bibliographically approved

Open Access in DiVA

fulltext(3926 kB)149 downloads
File information
File name FULLTEXT01.pdfFile size 3926 kBChecksum SHA-512
7b674d3b5defac9319981d96fbc768a5dc1ddc359c7c285851ef7a94e0cd82ee0a811001bc3445a1cba8f10066ec13681a42d3c4afa95aacd2fae47631b8fc5a
Type fulltextMimetype application/pdf

Other links

Publisher's full texthttp://pubs.rsc.org/en/content/articlelanding/2013/cp/c3cp51179k

Search in DiVA

By author/editor
Duarte, FernandaAmrein, Beat AntonKamerlin, Lynn
By organisation
Computational and Systems BiologyStructure and Molecular Biology
In the same journal
Physical Chemistry, Chemical Physics - PCCP
Theoretical Chemistry

Search outside of DiVA

GoogleGoogle Scholar
Total: 149 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 464 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf