Thermodynamic measurements of the solvation salts and electrolytes are relatively straightforward, but it is not possible to separate total free energies into distinct cation anion contributions without reference an additional extrathermodynamic assumption. The present work attempts resolve this difficulty using molecular dynamics simulations with AMOEBA polarizable force field perturbation techniques directly compute absolute for potassium, sodium, chloride ions in liquid water formamide....

Rhodopsin, the G protein-coupled receptor primarily responsible for sensing light, is found in an environment rich polyunsaturated lipid chains and cholesterol. Biophysical experiments have shown that unsaturation cholesterol both significant effects on rhodopsin's stability function; omega-3 chains, such as docosahexaenoic acid (DHA), destabilize rhodopsin enhance kinetics of photocycle, whereas has opposite effect. Here, we use molecular dynamics simulations to investigate possibility...

The alkaline earth metals calcium and magnesium are critically involved in many biomolecular processes. To understand the hydration thermodynamics of these ions, we have performed molecular dynamics simulations using a polarizable potential. Particle-mesh Ewald for point multipoles has been applied to calculation electrostatic interactions. parameters this model determined from an ab initio quantum mechanical dimer interactions between ions water. Two methods ion solvation free energy...

Recent isothiocyanate covalent labeling studies have suggested that a classical cannabinoid, (-)-7'-isothiocyanato-11-hydroxy-1',1'dimethylheptyl-hexahydrocannabinol (AM841), enters the cannabinoid CB2 receptor via lipid bilayer (Pei, Y., Mercier, R. W., Anday, J. K., Thakur, G. A., Zvonok, A. M., Hurst, D., Reggio, P. H., Janero, D. R., and Makriyannis, (2008) Chem. Biol. 15, 1207-1219). However, sequence of steps involved in such pathway entry has not yet been elucidated. Here, we test...

Abstract The central question in evaluating almost any result from a molecular dynamics simulation is whether the calculation has converged. Unfortunately, assessing ergodicity of single trajectory very difficult to do. In this work, we assess sampling simulations membrane protein rhodopsin by comparing results 26 independent trajectories, each run for 100 ns. By examining principal components and cluster populations, show that rhodopsin's fluctuations are not well described ns dynamics,...

The quantitative assessment of uncertainty and sampling quality is essential in molecular simulation. Many systems interest are highly complex, often at the edge current computational capabilities. Modelers must therefore analyze communicate statistical uncertainties so that "consumers'' simulated data understand its significance limitations. This article covers key analyses appropriate for trajectory generated by conventional simulation methods such as dynamics (single Markov chain) Monte...

The backbone dihedral parameters of the Amber RNA force field were improved by fitting using multiple linear regression to potential energies determined quantum chemistry calculations. Five and four glycosidic fit simultaneously reproduce a high-level density functional theory calculation (B97D3 with AUG-CC-PVTZ basis set). Umbrella sampling was used determine conformational free along angles, these better agree population conformations observed in protein data bank for new than conventional...

LOOS (Lightweight Object Oriented Structure‐analysis) is a C++ library designed to facilitate making novel tools for analyzing molecular dynamics simulations by abstracting out the repetitive tasks, allowing developers focus on scientifically relevant part of problem. supports input using native file formats most common biomolecular simulation packages, including CHARMM, NAMD, Amber, Tinker, and Gromacs. A dynamic atom selection language based C expression syntax included easily accessible...

Fengycin is a cyclic lipopeptide used as an agricultural fungicide. It synthesized by Bacillus subtilis immune response against fungal infection and functions damaging the target's cell membrane. Previous molecular dynamics simulations experiments have led to hypothesis that aggregation of fengycins on membrane surface plays key role in disruption. Here, we microsecond-scale all-atom understand specificity, selectivity, structure fengycin oligomers. Our suggest more likely form stable...

Evidence from a variety of spectroscopic probes indicates that (φ, ψ) values corresponding to the left-handed polyproline II helix (PII) are preferred for short alanine-based peptides in water. On basis results theoretical studies, it is believed observed preference dictated by favorable peptide−solvent interactions, which realized through formation optimal hydrogen-bonding water bridges between peptide donor and acceptor groups. In present study, we address this issue explicitly analyzing...

We present a 118-ns molecular dynamics simulation of rhodopsin embedded in bilayer composed 2:2:1 mixture 1-stearoyl-2-docosahexaenoyl-phosphatidylcholine (SDPC), 1-stearoyl-2-docosahexaenoyl-phosphatidylethanolamine (SDPE), and cholesterol, respectively. The demonstrates that the protein breaks lateral transverse symmetry bilayer. Lipids near preferentially reorient such their unsaturated chains interact with protein, while distribution cholesterol membrane complements variations...

The solvation of simple ions in water is studied using molecular dynamics simulations with a polarizable force field. Previous this potential demonstrated that anions are more favorably solvated than cations. present work an attempt to explain result by examining the effects on surrounding structure, particular focus first shell and its interactions water. We conclude while cations frustrated competition between ion-water water-water interactions, compatible good interactions.

Abstract An unresolved question about GPCR function is the role of membrane components in receptor stability and activation. In particular, cholesterol known to affect proteins, but details its effect on GPCRs are still elusive. Here, we describe how modulates behavior TM1‐TM2‐TM7‐helix 8(H8) functional network that comprises highly conserved NPxxY(x) 5,6 F motif, through specific interactions with receptor. The inferences based analysis microsecond length molecular dynamics (MD) simulations...

We have developed LOOS (Lightweight Object-Oriented Structure-analysis library) as an object-oriented library designed to facilitate the rapid development of tools for structural analysis simulations. supports native file formats most common simulation packages including AMBER, CHARMM, CNS, Gromacs, NAMD, Tinker, and X-PLOR. Encapsulation polymorphism are used simultaneously provide a stable interface programmer make easily extensible. A rich atom selection language based on C expression...

Abstract C. elegans react to metabolic distress caused by mismatches in oxygen and energy status via distinct behavioral responses. At the molecular level, these responses are coordinated under-characterized, redox-sensitive processes, thought initiate mitochondria. Complex I of electron transport chain is a major site reactive species (ROS) production canonically associated with oxidative damage following hypoxic exposure. Here, we use combination optogenetics CRISPR/Cas9-mediated genome...

Lipid nanoparticles (LNPs) containing ionizable aminolipids are among the leading platforms for successful delivery of nucleic-acid-based therapeutics, including messenger RNA (mRNA). The two recently FDA-approved COVID-19 vaccines developed by Moderna and Pfizer/BioNTech belong to this category. Ionizable aminolipids, cholesterol, DSPC lipids key components such formulations, crucially modulating physicochemical properties these formulations and, consequently, potency therapeutics. Despite...

Molecular dynamics (MD) is a powerful tool for understanding the fluctuations of biomolecular systems. It is, however, subject to statistical errors in its sampling underlying distribution states. One must understand these order draw meaningful conclusions from simulation. This becoming ever more critical as MD simulations even larger systems are attempted. We present here new method determining extent convergence that relies on measures fluctuation space sampled by simulation without any...

Understanding the functions of biomolecules requires insight not only from structures, but dynamics as well. Often, most interesting processes occur on time scales too slow for exploration by conventional molecular (MD) simulations. For this reason, alternative computational methods such elastic network models (ENMs) have become increasingly popular. These simple, coarse-grained represent molecules beads connected harmonic springs; system's motions are solved analytically normal mode...

Photoisomerization of the retinylidene chromophore rhodopsin is starting point in vision cascade. A counterion switch mechanism that stabilizes retinal protonated Schiff base (PSB) has been proposed to be an essential step activation. On basis vibrational and UV−visible spectroscopy, two models have emerged. In first model, PSB stabilized by Glu181 meta I state, while most recent proposal, it Glu113 as well Glu181. We assess these conducting a pair microsecond scale, all-atom molecular...