Enriched Conformational Sampling of DNA and Proteins with a Hybrid Hamiltonian Derived from the Protein Data Bank

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F18%3A00499418" target="_blank" >RIV/86652036:_____/18:00499418 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.3390/ijms19113405" target="_blank" >http://dx.doi.org/10.3390/ijms19113405</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms19113405" target="_blank" >10.3390/ijms19113405</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Enriched Conformational Sampling of DNA and Proteins with a Hybrid Hamiltonian Derived from the Protein Data Bank

Popis výsledku v původním jazyce

In this article, we present a method for the enhanced molecular dynamics simulation of protein and DNA systems called potential of mean force (PMF)-enriched sampling. The method uses partitions derived from the potentials of mean force, which we determined from DNA and protein structures in the Protein Data Bank (PDB). We define a partition function from a set of PDB-derived PMFs, which efficiently compensates for the error introduced by the assumption of a homogeneous partition function from the PDB datasets. The bias based on the PDB-derived partitions is added in the form of a hybrid Hamiltonian using a renormalization method, which adds the PMF-enriched gradient to the system depending on a linear weighting factor and the underlying force field. We validated the method using simulations of dialanine, the folding of TrpCage, and the conformational sampling of the Dickerson-Drew DNA dodecamer. Our results show the potential for the PMF-enriched simulation technique to enrich the conformational space of biomolecules along their order parameters, while we also observe a considerable speed increase in the sampling by factors ranging from 13.1 to 82. The novel method can effectively be combined with enhanced sampling or coarse-graining methods to enrich conformational sampling with a partition derived from the PDB.

Název v anglickém jazyce

Enriched Conformational Sampling of DNA and Proteins with a Hybrid Hamiltonian Derived from the Protein Data Bank

Popis výsledku anglicky

In this article, we present a method for the enhanced molecular dynamics simulation of protein and DNA systems called potential of mean force (PMF)-enriched sampling. The method uses partitions derived from the potentials of mean force, which we determined from DNA and protein structures in the Protein Data Bank (PDB). We define a partition function from a set of PDB-derived PMFs, which efficiently compensates for the error introduced by the assumption of a homogeneous partition function from the PDB datasets. The bias based on the PDB-derived partitions is added in the form of a hybrid Hamiltonian using a renormalization method, which adds the PMF-enriched gradient to the system depending on a linear weighting factor and the underlying force field. We validated the method using simulations of dialanine, the folding of TrpCage, and the conformational sampling of the Dickerson-Drew DNA dodecamer. Our results show the potential for the PMF-enriched simulation technique to enrich the conformational space of biomolecules along their order parameters, while we also observe a considerable speed increase in the sampling by factors ranging from 13.1 to 82. The novel method can effectively be combined with enhanced sampling or coarse-graining methods to enrich conformational sampling with a partition derived from the PDB.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

International Journal of Molecular Sciences

ISSN

1422-0067

e-ISSN

—

Svazek periodika

19

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

32

Strana od-do

—

Kód UT WoS článku

000451528500121

EID výsledku v databázi Scopus

2-s2.0-85055848129