Information theoretic measures for quantifying sequence-ensemble relationships of intrinsically disordered proteins
© The Author(s) 2019. Published by Oxford University Press..
Intrinsically disordered proteins (IDPs) contribute to a multitude of functions. De novo design of IDPs should open the door to modulating functions and phenotypes controlled by these systems. Recent design efforts have focused on compositional biases and specific sequence patterns as the design features. Analysis of the impact of these designs on sequence-function relationships indicates that individual sequence/compositional parameters are insufficient for describing sequence-function relationships in IDPs. To remedy this problem, we have developed information theoretic measures for sequence-ensemble relationships (SERs) of IDPs. These measures rely on prior availability of statistically robust conformational ensembles derived from all atom simulations. We show that the measures we have developed are useful for comparing sequence-ensemble relationships even when sequence is poorly conserved. Based on our results, we propose that de novo designs of IDPs, guided by knowledge of their SERs, should provide improved insights into their sequence-ensemble-function relationships.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2019 |
|---|---|
| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:32 |
|---|---|
| Enthalten in: |
Protein engineering, design & selection : PEDS - 32(2019), 4 vom: 31. Dez., Seite 191-202 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Cohan, Megan C [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 30.06.2020 Date Revised 04.09.2020 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1093/protein/gzz014 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM299871185 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM299871185 | ||
| 003 | DE-627 | ||
| 005 | 20231225101303.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1093/protein/gzz014 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0999.xml |
| 035 | |a (DE-627)NLM299871185 | ||
| 035 | |a (NLM)31375817 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Cohan, Megan C |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Information theoretic measures for quantifying sequence-ensemble relationships of intrinsically disordered proteins |
| 264 | 1 | |c 2019 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 30.06.2020 | ||
| 500 | |a Date Revised 04.09.2020 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2019. Published by Oxford University Press. | ||
| 520 | |a Intrinsically disordered proteins (IDPs) contribute to a multitude of functions. De novo design of IDPs should open the door to modulating functions and phenotypes controlled by these systems. Recent design efforts have focused on compositional biases and specific sequence patterns as the design features. Analysis of the impact of these designs on sequence-function relationships indicates that individual sequence/compositional parameters are insufficient for describing sequence-function relationships in IDPs. To remedy this problem, we have developed information theoretic measures for sequence-ensemble relationships (SERs) of IDPs. These measures rely on prior availability of statistically robust conformational ensembles derived from all atom simulations. We show that the measures we have developed are useful for comparing sequence-ensemble relationships even when sequence is poorly conserved. Based on our results, we propose that de novo designs of IDPs, guided by knowledge of their SERs, should provide improved insights into their sequence-ensemble-function relationships | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a computations | |
| 650 | 4 | |a ensemble entropy matrix | |
| 650 | 4 | |a intrinsically disordered proteins | |
| 650 | 4 | |a protein design | |
| 650 | 4 | |a sequence-ensemble relationships | |
| 650 | 7 | |a Intrinsically Disordered Proteins |2 NLM | |
| 700 | 1 | |a Ruff, Kiersten M |e verfasserin |4 aut | |
| 700 | 1 | |a Pappu, Rohit V |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Protein engineering, design & selection : PEDS |d 2004 |g 32(2019), 4 vom: 31. Dez., Seite 191-202 |w (DE-627)NLM146876229 |x 1741-0134 |7 nnns |
| 773 | 1 | 8 | |g volume:32 |g year:2019 |g number:4 |g day:31 |g month:12 |g pages:191-202 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1093/protein/gzz014 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 32 |j 2019 |e 4 |b 31 |c 12 |h 191-202 | ||