Noncovalent interactions, in particular the hydrogen bonds and nonspecific long-range electrostatic interactions are fundamental to biomolecular functions. A molecular understanding of local environment, consistently for both specific (hydrogen-bonding) (local polarity) is essential a detailed these processes. Vibrational Stark Effect (VSE) has proven be an extremely useful method measure electric field using infrared spectroscopy carbonyl nitrile based probes. The chemical group would ideal...

Significance Allosteric regulation is a crucial component in biochemical pathways, where ligand binding to an allosteric site modulates the enzymatic activity at distant functional site. There rapid growth interest toward rational design of drugs. PDZ domain proteins (frequently encountered signaling protein complexes) are classic examples allostery without significant structural changes (dynamic allostery), leads modulation distal side-chain motions. So far dynamic has been attributed...

Estimating rare event kinetics from molecular dynamics simulations is a non-trivial task despite the great advances in enhanced sampling methods. Weighted Ensemble (WE) simulation, special class of techniques, offers way to directly calculate kinetic rate constants biased trajectories without need modify underlying energy landscape using bias potentials. Conventional WE algorithms use different binning schemes partition collective variable (CV) space separating two metastable states...

In experimental studies, it has been observed that the presence of sodium dodecyl sulfate (SDS) significantly increases kinetics hydrate formation and final water-to-hydrate conversion ratio. this study, we intend to understand molecular mechanism behind effect SDS on methane through dynamics simulation. Hydrate conditions similar laboratory experiments were chosen study growth in 1 wt % solution. We also investigate interactions with isolated molecules growth. It was hydrophobic tail part...

Long-term storage and stability of DNA is paramount importance in biomedical applications. Ever since the emergence ionic liquids (ILs) as alternate green solvents to aqueous organic solvents, their exploration for extraction application need conscientious understanding binding characteristics molecular interactions between IL DNA. Choline amino acid ILs (CAAILs) this regard seem be promising due non-cytotoxic, completely biobased environment-friendly nature. To unravel key factors strength...

The demand for long-term storage and stability of proteins has increased substantially in the pharmaceutical industries, yet sensitivity toward environment become a cardinal task researchers. To deal with this, we have selected multifunctional enzyme Cytochrome-c (Cyt-c) involved many chemical biochemical reactions as model protein, which is very sensitive loses structural integrity on exposure to environment. remarkable features ionic liquids (ILs) entitled them alternatives aqueous organic...

Abstract The maintenance of machinery requires its operational understanding and a toolbox for repair. methods the precision engineering native proteins meet similar requirement in biosystems. Its success hinges on principles regulating chemical reactions with protein. Here, we report technology that delivers high-level control over reactivity, chemoselectivity, site-selectivity, modularity, dual-probe installation, protein-selectivity. It utilizes cysteine-based chemoselective...

Understanding the nature of free-energy surfaces for phosphate hydrolysis is a prerequisite understanding corresponding key chemical reactions in biology. Here, challenge has been to move careful ab initio QM/MM (QM(ai)/MM) calculations, where obtaining converging results very demanding and computationally expensive. This work describes such focusing on surface monoesters, paying special attention comparison between one water (1W) two (2W) paths proton-transfer (PT) step. issue explored...

Abstract Consistent description of the effect internal water in proteins has been a major challenge for both simulation and experimental studies. Describing this particularly important elusive cases charges protein interiors. Here, we present new microscopic method that provides an efficient way simulating energetics insertion. Instead performing explicit Monte Carlo (MC) moves on insertion process, which generally involves enormous number rejected attempts, our is based generating trial...

It has been suggested that the structure and thermodynamics of water molecules in hydration layer simple hydrophobic solutes undergo an order-disorder transition around a nanometer length-scale solute size. Using extensive atomistic molecular dynamics (MD) replica exchange (REMD) simulation studies, we have probed this model varying size shape (spherical, planar, linear), as well flexible homopolymer chains (n-alkanes), where conformational fluctuations are likely to create both spatial...

We have constructed a multidimensional free energy surface of nucleation the liquid phase from parent supercooled and supersaturated vapor near gas-liquid spinodal. In particular, we remove Becker-Doring constraint having only one growing cluster in system. Close to spinodal, energy, as function size largest cluster, develops surprisingly minimum at subcritical size. It is this intermediate that found be responsible for barrier towards further growth nucleus large supersaturation. An...

Cosolvents have versatile composition-dependent applications in chemistry and biology. The simultaneous presence of hydrophobic hydrophilic groups dimethyl sulfoxide (DMSO), an industrially important amphiphilic cosolvent, when combined with the unique properties water, plays key roles diverse fields pharmacology, cryoprotection, cell Moreover, molecules dissolved aqueous DMSO exhibit anomalous concentration-dependent nonmonotonic behavior stability activity near a critical mole fraction...

Glycopolypeptide-based polymersomes have promising applications as vehicles for targeted drug delivery because they are capable of encapsulating different pharmaceuticals diverse polarity well interacting with specific cell surfaces due to their hollow structural morphology and bioactive surfaces. We synthesized glycopolypeptide-b-poly(propylene oxide) by ROP glyco-N-carboxyanhydride (NCA) using the hydrophobic amine-terminated poly(propylene (PPO) initiator. This block copolymer is composed...

Misfolding and aggregation of prion proteins are associated with several neurodegenerative diseases. Therefore, understanding the mechanism misfolding process is enormous interest in scientific community. It has been speculated widely discussed that native cellular protein (PrPC) form needs to undergo substantial unfolding a more stable PrPC* state, which may further oligomerize into toxic scrapie (PrPSc) form. Here, we have studied human (huPrP) using set extensive well-tempered...

The structural basis of pathways misfolding a cellular prion (PrPC) into the toxic scrapie form (PrPSC) and identification possible intermediates (e.g., PrP*) still eludes us. In this work, we have used cumulative ∼65 μs replica exchange molecular dynamics simulation data to construct conformational free energy landscapes capture thermodynamic characteristics associated with various stages thermal denaturation process in human protein. temperature-dependent surfaces consist multiple...

Acetylcholinesterase (AChE) inhibitors are actively used for the effective treatment of Alzheimer's disease. In recent years, neuroprotective effects organoselenium compounds such as ebselen and diselenides on AChE activity have been investigated potential therapeutic agents. this work, we carried out systematic kinetic intrinsic fluorescence assays in combination with docking molecular dynamics (MD) simulations to elucidate mechanism mixed inhibition by diphenyl diselenide (DPDSe)...

Luminescent organic nanotubes derived from the co-assembly of cyanostilbene (CS) based cationic supramolecular polymers and bio-polyanion heparin, a known anticoagulant, have been utilized as highly efficient FRET (fluorescence resonance energy transfer) donors in aqueous media resulting amplified acceptor emission orange-red near-infrared (NIR). Energy transfer efficiencies higher than 80% an ultra-high antenna effect 150 were achieved even at high donor/acceptor ratios (500 : 1-100 1)...

We find that at a mole fraction 0.05 of DMSO (xDMSO = 0.05) in aqueous solution, linear hydrocarbon chain intermediate length (n 30–40) adopts the most stable collapsed conformation. In pure water, same exhibits an intermittent oscillation between and extended coiled conformations. Even when bulk is 0.05, concentration first hydration layer around 30 30) as large 17%. Formation such hydrophobic environment may be viewed reason for conformation gaining additional stability. second anomalous...

We show that the distance from interface at which bulk-like properties are recovered strongly depends on choice of order parameter being probed: translational < tetrahedral ≪ dipolar orientation.

The effect of few monovalent salts (NaCl, NH4Cl, and GdmCl) as additives, according to the Hofmeister series on growth methane gas hydrates, has been studied using experiments well molecular dynamics (MD) simulation. Further, effects hydrate crystallization have correlated with methanol an additive, which is a known thermodynamic inhibitor for growth. One previous studies (discussed later in this article) available literature concludes that formation from ice might show enhanced kinetics...

Using systematic molecular dynamics (MD) simulations, we revisit the question: At what distance from an interface do properties of "bulk water" get recovered? We have considered three different kinds interfaces: nonpolar (hydrophobic; isooctane–water interface), charged (negative; AOT bilayer), and polar (zwitterionic; POPC bilayer). In order to interrogate extent perturbation interfacial water molecules as a function interface, utilize diverse range structural dynamical parameters. To...