J 2020

Choice of Force Field for Proteins Containing Structured and Intrinsically Disordered Regions

ZAPLETAL, Vojtěch, Arnošt MLÁDEK, Kateřina BENDOVÁ, Petr LOUŠA, Erik NOMILNER et. al.

Basic information

Original name

Choice of Force Field for Proteins Containing Structured and Intrinsically Disordered Regions

Authors

ZAPLETAL, Vojtěch (203 Czech Republic, belonging to the institution), Arnošt MLÁDEK (203 Czech Republic, belonging to the institution), Kateřina BENDOVÁ (203 Czech Republic, belonging to the institution), Petr LOUŠA (203 Czech Republic, belonging to the institution), Erik NOMILNER (703 Slovakia, belonging to the institution), Zuzana JASEŇÁKOVÁ (703 Slovakia, belonging to the institution), Vojtěch KUBÁŇ (203 Czech Republic, belonging to the institution), Markéta MAKOVICKÁ (203 Czech Republic, belonging to the institution), Alice LANÍKOVÁ (203 Czech Republic, belonging to the institution), Lukáš ŽÍDEK (203 Czech Republic, belonging to the institution) and Jozef HRITZ (703 Slovakia, guarantor, belonging to the institution)

Edition

Biophysical Journal, Bethesda, USA, Biophysical Society, 2020, 0006-3495

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10610 Biophysics

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 4.033

RIV identification code

RIV/00216224:14740/20:00115635

Organization unit

Central European Institute of Technology

DOI

UT WoS

000524456100012

Keywords in English

MOLECULAR-DYNAMICS; TYROSINE-HYDROXYLASE; NMR RELAXATION; RNA-POLYMERASE; DELTA-SUBUNIT; PREDICTION; PHOSPHORYLATION; RECOGNITION; ALIGNMENT; BIOLOGY

Tags

Tags

International impact, Reviewed
Změněno: 14/10/2024 13:27, Ing. Jana Kuchtová

Abstract

V originále

Biomolecular force fields optimized for globular proteins fail to properly reproduce properties of intrinsically disordered proteins. In particular, parameters of the water model need to be modified to improve applicability of the force fields to both ordered and disordered proteins. Here, we compared performance of force fields recommended for intrinsically disordered proteins in molecular dynamics simulations of three proteins differing in the content of ordered and disordered regions (two proteins consisting of a well-structured domain and of a disordered region with and without a transient helical motif and one disordered protein containing a region of increased helical propensity). The obtained molecular dynamics trajectories were used to predict measurable parameters, including radii of gyration of the proteins and chemical shifts, residual dipolar couplings, paramagnetic relaxation enhancement, and NMR relaxation data of their individual residues. The predicted quantities were compared with experimental data obtained within this study or published previously. The results showed that the NMR relaxation parameters, rarely used for benchmarking, are particularly sensitive to the choice of force-field parameters, especially those defining the water model. Interestingly, the TIP3P water model, leading to an artificial structural collapse, also resulted in unrealistic relaxation properties. The TIP4P-D water model, combined with three biomolecular force-field parameters for the protein part, significantly improved reliability of the simulations. Additional analysis revealed only one particular force field capable of retaining the transient helical motif observed in NMR experiments. The benchmarking protocol used in our study, being more sensitive to imperfections than the commonly used tests, is well suited to evaluate the performance of newly developed force fields.

Links

LM2015085, research and development project
Name: CERIT Scientific Cloud (Acronym: CERIT-SC)
Investor: Ministry of Education, Youth and Sports of the CR, CERIT Scientific Cloud
LQ1601, research and development project
Name: CEITEC 2020 (Acronym: CEITEC2020)
Investor: Ministry of Education, Youth and Sports of the CR
LTAUSA18168, research and development project
Name: Selektivní NMR značení jako nástroj pro charakterizaci proteinových komplexů zapojených do neurodegenerativních onemocnění
Investor: Ministry of Education, Youth and Sports of the CR, Selective NMR labelling as a tool for characterization of protein complexes involved in neurodegenerative diseases., INTER-ACTION
LTC17078, research and development project
Name: Studium interakcí domén přirozeně neuspořádaného proteinu MAP2c (microtubule- associated protein 2c) s jeho vazebnými partnery pomocí výpočetních metod a nukleární magnetické rezonance
Investor: Ministry of Education, Youth and Sports of the CR, Study of domain interactions of intrinsically disordered protein MAP2c (Microtubule-Associated Protein 2c) with its binding partners via computational methods and nuclear magnetic resonance, INTER-COST
90042, large research infrastructures
Name: CESNET II
90070, large research infrastructures
Name: IT4Innovations
90127, large research infrastructures
Name: CIISB II