Developing and Benchmarking Sulfate and Sulfamate Force Field Parameters via Ab Initio Molecular Dynamics Simulations To Accurately Model Glycosaminoglycan Electrostatic Interactions

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F24%3A00598061" target="_blank" >RIV/61388963:_____/24:00598061 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14740/24:00138324

Result on the web

<a href="https://doi.org/10.1021/acs.jcim.4c00981" target="_blank" >https://doi.org/10.1021/acs.jcim.4c00981</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jcim.4c00981" target="_blank" >10.1021/acs.jcim.4c00981</a>

Result language

angličtina

Original language name

Developing and Benchmarking Sulfate and Sulfamate Force Field Parameters via Ab Initio Molecular Dynamics Simulations To Accurately Model Glycosaminoglycan Electrostatic Interactions

Original language description

Glycosaminoglycans (GAGs) are negatively charged polysaccharides found on cell surfaces, where they regulate transport pathways of foreign molecules toward the cell. The structural and functional diversity of GAGs is largely attributed to varied sulfation patterns along the polymer chains, which makes understanding their molecular recognition mechanisms crucial. Molecular dynamics (MD) simulations, thanks to their unmatched microscopic resolution, have the potential to be a reference tool for exploring the patterns responsible for biologically relevant interactions. However, the capability of molecular dynamics force fields used in biosimulations to accurately capture sulfation-specific interactions is not well established, partly due to the intrinsic properties of GAGs that pose challenges for most experimental techniques. In this work, we evaluate the performance of molecular dynamics force fields for sulfated GAGs by studying ion pairing of Ca2+ to sulfated moieties─N-methylsulfamate and methylsulfate─that resemble N- and O-sulfation found in GAGs, respectively. We tested available nonpolarizable (CHARMM36 and GLYCAM06) and explicitly polarizable (Drude and AMOEBA) force fields, and derived new implicitly polarizable models through charge scaling (prosECCo75 and GLYCAM-ECC75) that are consistent with our developed “charge-scaling” framework. The calcium–sulfamate/sulfate interaction free energy profiles obtained with the tested force fields were compared against reference ab initio molecular dynamics (AIMD) simulations, which serve as a robust alternative to experiments. AIMD simulations indicate that the preferential Ca2+ binding mode to sulfated GAG groups is solvent-shared pairing. Only our scaled-charge models agree satisfactorily with the AIMD data, while all other force fields exhibit poorer agreement, sometimes even qualitatively. Surprisingly, even explicitly polarizable force fields display a notable disagreement with the AIMD data, likely attributed to difficulties in their optimization and possible inherent limitations in depicting high-charge-density ion interactions accurately. Finally, the underperforming force fields lead to unrealistic aggregation of sulfated saccharides, which qualitatively disagrees with our understanding of the soft glycocalyx environment. Our results highlight the importance of accurately treating electronic polarization in MD simulations of sulfated GAGs and caution against over-reliance on currently available models without thorough validation and optimization.

Czech name

—

Czech description

—

Type

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

CEP classification

—

OECD FORD branch

10403 - Physical chemistry

Project

<a href="/en/project/GA24-11274S" target="_blank" >GA24-11274S: Tailoring polymeric implant coatings against bacteria attachment: a knowledge-based approach</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

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

Name of the periodical

Journal of Chemical Information and Modeling

ISSN

1549-9596

e-ISSN

1549-960X

Volume of the periodical

64

Issue of the periodical within the volume

18

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

7122-7134

UT code for WoS article

001309504100001

EID of the result in the Scopus database

2-s2.0-85204052984