Carbohydrate Force Fields: The Role of Small Partial Atomic Charges in Preventing Conformational Collapse
Ryan D Lazar1, Farideh B Akher1, Neil Ravenscroft2
1Department of Computer Science, University of Cape Town, Rondebosch, Cape Town 7701, South Africa.
Journal of Chemical Theory and Computation
|January 11, 2022
Summary
Molecular dynamics simulations reveal that the GLYCAM06j force field can cause polysaccharide collapse due to missing charges on aliphatic hydrogens in rhamnose. Adding these charges resolves the issue, improving force field accuracy for carbohydrate simulations.
Area of Science:
- Computational chemistry
- Biomolecular modeling
- Carbohydrate chemistry
Background:
- Additive all-atom force fields are crucial for modeling carbohydrate behavior.
- Previous studies noted discrepancies in simulated hydrodynamic properties of polysaccharides using different force fields.
- The GLYCAM06j force field has been associated with irreversible conformational collapse in certain polysaccharide simulations.
Purpose of the Study:
- To investigate the cause of conformational collapse observed in polysaccharide simulations using the GLYCAM06j force field.
- To compare the behavior of saccharides simulated with GLYCAM06j and CHARMM36 carbohydrate force fields.
- To identify specific molecular features responsible for the observed simulation artifacts.
Main Methods:
- Comparative molecular dynamics simulations of various saccharides using GLYCAM06j and CHARMM36 force fields.
- Analysis of conformational changes and energy profiles of glycosidic linkages.
- Quantum mechanical calculations for comparison with force field results.
- Systematic modification of the GLYCAM06j force field by adding partial charges to aliphatic hydrogens.
Main Results:
- Conformational collapse was observed in GLYCAM06j simulations of polysaccharides containing the deoxy sugar α-l-rhamnose, particularly after long simulation times.
- The collapse mechanism was traced to an anomalously low energy of specific α-l-Rha to α-l-Rha glycosidic linkages in GLYCAM06j compared to quantum mechanical calculations.
- This low energy was attributed to the absence of partial charges on aliphatic hydrogens in the GLYCAM force field.
- Adding partial charges to the aliphatic protons in rhamnose successfully eliminated the conformational collapse phenomenon.
Conclusions:
- The lack of partial charges on aliphatic hydrogens in the GLYCAM force field is responsible for the conformational collapse of certain polysaccharides.
- Small partial charges can have a significant cumulative effect on the dynamic behavior of polysaccharides.
- Future reparameterization of the GLYCAM06j force field should consider incorporating partial charges on all aliphatic hydrogens to enhance accuracy.
Related Concept Videos
02:35Noncovalent Attractions in Biomolecules
58.4K
Noncovalent attractions are associations within and between molecules that influence the shape and structural stability of complexes. These interactions differ from covalent bonding in that they do not involve sharing of electrons.
Four types of noncovalent interactions are hydrogen bonds, van der Waals forces, ionic bonds, and hydrophobic interactions.
Hydrogen bonding results from the electrostatic attraction of a hydrogen atom covalently bonded to a strong-electronegative atom like oxygen,...
Four types of noncovalent interactions are hydrogen bonds, van der Waals forces, ionic bonds, and hydrophobic interactions.
Hydrogen bonding results from the electrostatic attraction of a hydrogen atom covalently bonded to a strong-electronegative atom like oxygen,...
58.4K
01:22Protein Folding
123.1K
Overview
123.1K
02:11Conformations of Cyclohexane
13.7K
Cyclohexane does not exist in a planar form due to the high angle and torsional strain it would experience in the planar structure. Instead, it adopts non-planar chair and boat conformations.
The chair form is the most stable and derives its name from its resemblance to the “easy chair.” In the chair conformation, two carbon atoms are arranged out-of-plane — one above and one below, minimizing the torsional strain. In the chair form, the bond angle is very close to the ideal...
The chair form is the most stable and derives its name from its resemblance to the “easy chair.” In the chair conformation, two carbon atoms are arranged out-of-plane — one above and one below, minimizing the torsional strain. In the chair form, the bond angle is very close to the ideal...
13.7K
00:52¹H NMR of Conformationally Flexible Molecules: Temporal Resolution
949
At room temperature, the chair conformer of cyclohexane undergoes rapid ring flipping between two equivalent chair conformers at a rate of approximately 105 times per second. These two chair conformers are in equilibrium. The rapid ring flipping results in the interconversion of the axial proton to an equatorial proton and an equatorial to the axial proton. Such interconversions are too rapid and cannot be detected on the NMR timescale. Hence, the NMR spectrometer cannot distinguish between the...
949
01:24Van der Waals Interactions
67.3K
Atoms and molecules interact with each other through intermolecular forces. These electrostatic forces arise from attractive or repulsive interactions between particles with permanent, partial, or temporary charges. The intermolecular forces between neutral atoms and molecules are ion–dipole, dipole–dipole, and dispersion forces, collectively known as van der Waals forces.
67.3K
02:19Lewis Structures and Formal Charges
17.1K
Lewis symbols can be used to indicate the formation of covalent bonds, which are shown in Lewis structures—drawings that describe the bonding in molecules and polyatomic ions. The periodic table can be used to predict the number of valence electrons in an atom and the number of bonds that will be formed to reach an octet. Group 18 elements, such as argon and helium, have filled electron configurations and thus rarely participate in chemical bonding. However, atoms from group 17, such as...
17.1K