Can All-Atom Molecular Dynamics Simulations Quantitatively Describe Homeodomain-DNA Binding Equilibria?

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F19%3A00504470" target="_blank" >RIV/61388963:_____/19:00504470 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11310/19:10409808

Result on the web

<a href="https://pubs.acs.org/doi/10.1021/acs.jctc.8b01144" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jctc.8b01144</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jctc.8b01144" target="_blank" >10.1021/acs.jctc.8b01144</a>

Result language

angličtina

Original language name

Can All-Atom Molecular Dynamics Simulations Quantitatively Describe Homeodomain-DNA Binding Equilibria?

Original language description

We systematically investigate the applicability of a molecular dynamics-based setup for the calculations of standard binding free energies of biologically relevant protein-DNA complexes. The free energies are extracted from a potential of mean force calculated using umbrella sampling simulations. Two protein-DNA systems derived from a homeodomain transcription factor complex are studied in order to investigate the binding of both disordered and globular proteins. Free energies and trajectories obtained using two modern molecular mechanical force fields are compared to each other and to experimental data. The temperature dependence of the calculated standard binding free energies is investigated by performing all simulations over a range of temperatures. We show that the values of standard binding free energies obtained from these simulations are overestimated compared to experimental results. Significant differences are observed between the two protein-DNA systems and between the two force fields, which are explained by different propensities to form inter- and intramolecular contacts. The number of protein-DNA contacts increases with increasing temperature, in agreement with the experimentally known temperature dependence of enthalpies of binding. However, conclusions about the temperature dependence of the standard binding free energies cannot be made with confidence, as the differences among the values are on the order of statistical uncertainty.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10403 - Physical chemistry

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

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

Publication year

2019

Confidentiality

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

Name of the periodical

Journal of Chemical Theory and Computation

ISSN

1549-9618

e-ISSN

—

Volume of the periodical

15

Issue of the periodical within the volume

4

Country of publishing house

US - UNITED STATES

Number of pages

14

Pages from-to

2635-2648

UT code for WoS article

000464475500043

EID of the result in the Scopus database

2-s2.0-85064167869