We present a refined Drude polarizable carbohydrate force field (FF) for hexopyranose monosaccharides, improving ring and exocyclic torsional parameters to address discrepancies with experimental NMR 3J coupling values. This refinement focuses on major hexose monosaccharides and their anomers (e.g., α/β-MAN, GLC, GAL, ALT, IDO). The optimization used quantum mechanical (QM) potential energy scans (PES) for ring and exocyclic dihedrals. Validated against experimental NMR data and conformational energetics in aqueous solutions, the updated model provides better agreement with QM data and offers enhanced accuracy for simulating carbohydrate conformational dynamics, advancing Drude carbohydrate FF performance in biomolecular simulations.

The discovery of graphene ushered in a new era in multiple domains of scientific research. The relative ease of large- scale synthesis and the unique physiochemical properties of graphene led many research groups to investigate the applicability of graphene as a functional material for a broad spectrum of applications. Here we review the applications of graphene in two broad areas: as an atomistically thin solid support assisting the formation of self-assembled monolayers and as a functional material for DNA sequencing. 

Elucidating the atomistic intricacies governing pore clogging is pivotal to devising strategies for its mitigation and advancing our understanding of graphene nanopore behavior. We harness Drude polarizable simulations to systematically dissect the nucleobase-dependent mechanisms that play a pivotal role in nanopore clogging. We unveil nucleobase-specific interactions that illuminate the multifaceted roles played by both hydrophobic and electrostatic forces in driving nanopore clogging events. Notably, the Drude simulations also unveil the bias-dependent translocation dynamics and its pivotal role in alleviating pore clogging─a facet that remains significantly underestimated in conventional additive (nonpolarizable) simulations. 

Our results utilizing the Drude polarizable force field (FF) for ions, water and graphene surfaces show that the simulations accurately capture the dynamics at the electrolyte–graphene interface. For monovalent ions, with increasing size, the solvation shell plays a crucial role in controlling the ion–graphene interactions. Smaller monovalent ions directly interact with the graphene surface, while larger ions interact with the graphene surface via a well-formed solvation shell. For divalent ions, both interaction modes are observed. For the anion Cl−, we observe direct interaction between the ions and the graphene surface. The anion–graphene interactions are strongly driven by the polarizability of the graphene surface. 

In this study, we analyze the influence of the polarizable force field on the ring dynamics of five major types of unsubstituted aldohexoses─glucose, mannose, galactose, altrose, and idose and their anomers. Our studies reveal that the inclusion of polarization enhances the sampling of ring conformations and lowers the energy barriers between the 4C1 and 1C4 conformations. Overall, the CHARMM36 additive force field is observed to be rigid and favors the 4C1 conformations. Although the inclusion of polarizability results in enhancing ring flexibility, we observe sampling that does not agree with experimental results, warranting a revision of the polarizable Drude parameters.

We show that a polarizable force field can accurately capture the spontaneous self-assembly of higher-order structures in cytosine nucleobases that cannot be captured by nonpolarizable force fields. A gradual transition from an ordered 2D network to a sizable disordered network of hydrogen-bonded structures was observed upon increasing the concentration of nucleobases from 0.25 to 0.75 M. 

Antimicrobial peptides (AMPs) are naturally occurring promising candidates which can be used as antibiotics against a wide variety of bacteria. However, the molecular details of their mechanism of action is not yet fully understood. In this study, we try to shed light on the mode of action of AMPs, possible reason behind it, and their interaction with lipid bilayers through experimental as well as molecular dynamics (MD) simulation studies. 

Helices (α-helix) are the most common type of secondary structure motif present in proteins. In this study, we investigated the structural influence of phosphorylation and O-GlcNAcylation, common intracellular post-translational modifications (PTMs), on the α-helical conformation. The simulation studies were performed on the Baldwin model α-helical peptide sequence (Ac-AKAAAAKAAAAKAA-NH2). 

Taupathies involve the deposition of abnormal tau protein into neurofibrillary tangles (NFTs) in the human brain. The abnormally hyperphosphorylated tau dissociates from microtubules and forms insoluble aggregates known as paired helical filaments (PHFs), highlighting the importance of post-translational modifications in taupathies. The present study examined the factors responsible for the structural stability of PHFs in native as well as in phosphorylated and O-GlcNAcylated tau.

We reported the development of Drude parameters for describing the polarizable graphene sheet compatible with the CHARMM Polarizable Force Field. The developed parameters were used to study the self-aggregation phenomenon of nucleobases on a graphene support. Two of the key observations were the probability of the formation of stacks in guanine-rich systems, and the spontaneous formation of H-bonded structures over the graphene sheet, which allude to the importance of the DNA sequence and composition. Both these effects were not observed in the additive simulations.

How specific phosphorylation and/or O-GlcNAcylation events influence Tau conformations remains largely unknown due to the disordered nature of Tau. In this study, we have investigated the phosphorylation- and O-GlcNAcylation-induced conformational effects on a Tau segment (Tau225–246) from the proline-rich domain (P2), by performing metadynamics simulations. We find that phosphorylation leads to the formation of strong salt-bridge contacts with adjacent lysine and arginine residues, which disrupts the native β-sheet structure observed in Tau225–246.

We proposed the newly discovered 2D boron sheets (α, α1 and β1 sheets) as a promising adsorbate material for DNA fingerprinting applications. The relatively high binding energies of the DNA bases Adenine (A), thymine (T), guanine (G) and cytosine (C) and the DNA base pairs A:T and G:C on the sheets suggest stabilization of the DNA constructs on these sheets.

Antifreeze glycoproteins (AFGPs) are distinctively riveting class of bio-macromolecules, which endows the survival of organisms inhabiting polar and subpolar regions. These proteins are believed to hinder microscopic freezing by interacting with embryonic ice crystals and precluding their further growth. The underlying molecular mechanism by which AFGPs bind to ice has remained elusive due to insufficient structural characterization, with conflicting hypotheses on the possible binding mode of AFGPs – either via the hydrophobic peptide backbone or via the hydrophilic carbohydrate side chains – when interacting with ice. In this study, we used molecular dynamics (MD) simulations to probe the microscopic properties of water accompanying these structural variations of AFGPs.

In this work, we reported the development of Drude polarizable force field parameters for the carboxylate and N-acetyl amine derivatives, extending the functionality of the existing Drude polarizable carbohydrate force field. The parameter development resulted in the incorporation of d-glucuronate, l-iduronate, N-acetyl-d-glucosamine (GlcNAc), and N-acetyl-d-galactosamine (GalNAc) sugars into the CHARMM Drude polarizable force field.

Cell-penetrating peptides (CPPs) facilitate the transport of pharmacologically active molecules, such as plasmid DNA, short interfering RNA, nanoparticles, and small peptides. The accurate identification of new and unique CPPs is the initial step to gain insight into CPP activity. The synthesis and identification of CPPs through wet-lab experiments is both resource- and time-expensive. Therefore, the development of an efficient prediction tool is essential for the identification of unique CPP prior to experiments. To this end, we developed a kernel extreme learning machine (KELM) based CPP prediction model called KELM-CPPpred.

Phosphorylation and O-GlcNAcylation are rapidly cycling intracellular protein post-translational modifications (PTMs) that can compete for the same serine (S) and threonine (T) sites. Limited crystal structure information is available on the direct influence of these PTMs on the underlying protein structure, especially for O-GlcNAcylation. NMR and CD studies show that these competitive-PTMs can have the same or differential influence on the overall secondary structure. In the absence of substantial structural information, we have performed a systematic computational study utilizing PDB analysis, QM calculations, and MD simulations to identify key structural trends upon PTM.

Carbohydrates are known to closely modulate their surrounding solvent structures and influence solvation dynamics. Spectroscopic investigations studying far-IR regions (below 1000 cm–1) have observed spectral shifts in the libration band (around 600 cm–1) of water in the presence of monosaccharides and polysaccharides. In this paper, we used molecular dynamics simulations to gain atomistic insight into carbohydrate–water interactions and to specifically highlight the differences between additive (nonpolarizable) and polarizable simulations.