Improving the Path to Obtain Spectroscopic Parameters for the PI3K—(Platinum Complex) System: Theoretical Evidences for Using 195Pt NMR as a Probe

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F23%3A50020401" target="_blank" >RIV/62690094:18470/23:50020401 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.mdpi.com/2312-7481/9/4/89" target="_blank" >https://www.mdpi.com/2312-7481/9/4/89</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/magnetochemistry9040089" target="_blank" >10.3390/magnetochemistry9040089</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Improving the Path to Obtain Spectroscopic Parameters for the PI3K—(Platinum Complex) System: Theoretical Evidences for Using 195Pt NMR as a Probe

Popis výsledku v původním jazyce

The absence of adequate force field (FF) parameters to describe certain metallic complexes makes new and deeper analyses impossible. In this context, after a group of researchers developed and validated an AMBER FF for a platinum complex (PC) conjugated with AHBT, new possibilities emerged. Thus, in this work, we propose an improved path to obtain NMR spectroscopic parameters, starting from a specific FF for PC, allowing to obtain more reliable information and a longer simulation time. Initially, a docking study was carried out between a PC and PI3K enzyme, aiming to find the most favorable orientation and, from this pose, to carry out a simulation of classical molecular dynamics (MD) with an explicit solvent and simulation time of 50 ns. To explore a new PC environment, a second MD simulation was performed only between the complex and water molecules, under the same conditions as the first MD. After the results of the two MDs, we proposed strategies to select the best amino acid residues (first MD) and water molecules (second MD) through the analyses of hydrogen bonds and minimum distance distribution functions (MDDFs), respectively. In addition, we also selected the best frames from the two MDs through the OWSCA algorithm. From these resources, it was possible to reduce the amount and computational cost of subsequent quantum calculations. Thus, we performed NMR calculations in two chemical environments, enzymatic and aqueous, with theory level GIAO–PBEPBE/NMR-DKH. So, from a strategic path, we were able to obtain more reliable chemical shifts and, therefore, propose safer spectroscopic probes, showing a large difference between the values of chemical shifts in the enzymatic and aqueous environments. © 2023 by the authors.

Název v anglickém jazyce

Improving the Path to Obtain Spectroscopic Parameters for the PI3K—(Platinum Complex) System: Theoretical Evidences for Using 195Pt NMR as a Probe

Popis výsledku anglicky

The absence of adequate force field (FF) parameters to describe certain metallic complexes makes new and deeper analyses impossible. In this context, after a group of researchers developed and validated an AMBER FF for a platinum complex (PC) conjugated with AHBT, new possibilities emerged. Thus, in this work, we propose an improved path to obtain NMR spectroscopic parameters, starting from a specific FF for PC, allowing to obtain more reliable information and a longer simulation time. Initially, a docking study was carried out between a PC and PI3K enzyme, aiming to find the most favorable orientation and, from this pose, to carry out a simulation of classical molecular dynamics (MD) with an explicit solvent and simulation time of 50 ns. To explore a new PC environment, a second MD simulation was performed only between the complex and water molecules, under the same conditions as the first MD. After the results of the two MDs, we proposed strategies to select the best amino acid residues (first MD) and water molecules (second MD) through the analyses of hydrogen bonds and minimum distance distribution functions (MDDFs), respectively. In addition, we also selected the best frames from the two MDs through the OWSCA algorithm. From these resources, it was possible to reduce the amount and computational cost of subsequent quantum calculations. Thus, we performed NMR calculations in two chemical environments, enzymatic and aqueous, with theory level GIAO–PBEPBE/NMR-DKH. So, from a strategic path, we were able to obtain more reliable chemical shifts and, therefore, propose safer spectroscopic probes, showing a large difference between the values of chemical shifts in the enzymatic and aqueous environments. © 2023 by the authors.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

Magnetochemistry

ISSN

2312-7481

e-ISSN

2312-7481

Svazek periodika

9

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

12

Strana od-do

"Article number: 89"

Kód UT WoS článku

000978173000001

EID výsledku v databázi Scopus

2-s2.0-85153936308