Abstract MDAnalysis is an object‐oriented library for structural and temporal analysis of molecular dynamics (MD) simulation trajectories individual protein structures. It written in the Python language with some performance‐critical code C. uses powerful NumPy package to expose trajectory data as fast efficient arrays. has been tested on systems millions particles. Many common file formats packages including CHARMM, Gromacs, Amber, NAMD Protein Data Bank format can be read written. Atoms...

The microscopic details of lipid–protein interactions are examined using molecular dynamics simulations the gramicidin A channel embedded in a fully hydrated dimyristoyl phosphatidylcholine (DMPC) bilayer. novel construction protocol was used to assemble initial configurations membrane protein complex for simulations. Three hundreds systems were constructed with different lipid placement and conformations. Seven simulated dynamics. One system total 600 psec, four 300 two 100 psec. Analysis...

A molecular dynamics simulation of the gramicidin channel in an explicit dimyristoyl phosphatidylcholine bilayer was generated to study details lipid-protein interactions at microscopic level. Solid-state NMR properties averaged over 500-psec trajectory are excellent agreement with available experimental data. In contrast assumptions macroscopic models, membrane/solution interface region is found be least 12 thick. The tryptophan side chains, located within interface, form hydrogen bonds...

We present coarse-grained simulations of fusion between two liposomes from which a detailed picture lipid movements emerges. In these the bilayers dilate at contact edge, and resulting increase in area per produces tilting individual molecules as predicted. Fusion is initiated when some tilted lipids splay their aliphatic tails, such that are shared opposing leaflets. Multiple splayed subsequently associate with tails contact, new hydrophobic core. As extend into more parallel conformation...

We present all-atom molecular dynamics simulations of biologically realistic transmembrane potential gradients across a DMPC bilayer. These are the first to model this gradient in detail, with field generated solely by explicit ion dynamics. Unlike traditional bilayer that have one per unit cell, we simulate 170 mV using cell consisting three salt-water baths separated two bilayers, full three-dimensional periodicity. The study shows current computational resources powerful enough generate...

Systematic inaccuracy is inherent in any computational estimate of a non-linear average, due to the availability only finite number data values, N. Free energy differences (DF) between two states or systems are critically important examples such averages physical, chemical and biological settings. Previous work has demonstrated, empirically, that ``finite-sampling error'' can be very large -- many times kT DF estimates for simple molecular systems. Here, we present theoretical description...

A challenge in free energy calculation for complex molecular systems by computer simulation is to obtain a reliable estimate within feasible computational time. In this study, we suggest an answer exploring simple method, overlap sampling (OS), producing free-energy results efficient way. The formalism of the OS method based on ensuring important overlapping phase space during perturbation calculations. This technique samples both forward and reverse (FEP) improve calculation. It considers...

A set of all-atom molecular dynamics simulations have been performed to better understand critical phenomena regarding a Hofmeister series anions and lipid bilayers. The isolate the effect anion size show clear differences in interactions with dipolar phoshpatidylcholine headgroup. Cl- penetrate into headgroup region bilayer, but confirm theories which predict that larger more deeply, heterogeneous hydrophobic region. That leads such partitioning bilayer provides atomic-level support...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTConformational Flexibility of o-Phosphorylcholine and o-Phosphorylethanolamine: A Molecular Dynamics Study Solvation EffectsThomas B. Woolf Benoit RouxCite this: J. Am. Chem. Soc. 1994, 116, 13, 5916–5926Publication Date (Print):June 1, 1994Publication History Published online1 May 2002Published inissue 1 June 1994https://pubs.acs.org/doi/10.1021/ja00092a048https://doi.org/10.1021/ja00092a048research-articleACS PublicationsRequest reuse...

Intrinsically disordered proteins are an important class of with unique functions and properties. Here, we have applied a support vector machine (SVM) trained on naturally occurring ordered to examine the contribution various parameters (vectors) recognizing that contain regions. We find SVM incorporates only amino acid composition has recognition accuracy 87 ± 2%. This result suggests alone is sufficient accurately recognize disorder. Interestingly, SVMs using reduced sets acids based...

We implement the replica exchange molecular dynamics algorithm to study interactions of a model peptide (WALP-16) with an explicitly represented DPPC membrane bilayer. observe spontaneous, unbiased insertion WALP-16 into bilayer and its folding α-helix transbilayer orientation. The free energy surface suggests that precedes secondary structure formation. Although has some propensity form partially helical in interfacial region DPPC/water system, this state is not productive intermediate but...

An all-atom molecular dynamics simulation of rhodopsin in a membrane environment has been carried out with lipid composition similar to that the retinal membrane. The initial conformation protein was taken from X-ray crystallographic structure (1F88), while those lipids came previous simulation. During course 12.5 ns simulation, initially randomly placed adopt an anisotropic solvation around protein. lipids, having one saturated stearic acid chain and polyunsaturated docosohexaenoic...

Background We aim to evaluate the association between meal intervals and weight trajectory among adults from a clinical cohort. Methods Results This is multisite prospective cohort study of recruited 3 health systems. Over 6-month period, 547 participants downloaded used mobile application record timing meals sleep for at least 1 day. obtained information on comorbidities each outpatient visit electronic records up 10 years before until months after baseline. mixed linear regression model...

We have solubilized and purified the histidine-tagged yeast secretory pathway/Golgi ion pump Pmr1 to near homogeneity in one step, using nickel affinity chromatography. The demonstrates both Ca2+- Mn2+-dependent ATP hydrolysis phosphoenzyme intermediate formation forward (ATP) reverse (Pi) directions. This preparation has allowed us examine, detail, properties of mutations D778A Q783A transmembrane segment M6 Pmr1. In phenotypic screens Ca2+ chelator Mn2+ toxicity reported separately (Wei,...

We extend a previously developed method, based on Wagner’s stochastic formulation of importance sampling, to the calculation reaction rates and simple quantitative description finite-temperature, average dynamic paths. Only initial final states are required as input—no information transition state(s) is necessary. demonstrate method for single particle moving two-dimensional Müller–Brown potential surface. Beyond computing forward reverse this surface, we determine path, which exhibits...

Abstract The Morphology of olfactory bulb granule cell spines and their dendrodendritic synaptic relations with mitral tufted dendrites were examined using serial electron micrographs 3D computer reconstructions. Most pedunculated large elliptical heads necks (stems) longer than those described for exclusively postsynaptic elsewhere in the nerous system. typically contained a mitochondrion, which most likely reflects metabolic requirements presynaptic functions these spines. In several cases...

Membrane protein structure and function are influenced by the interaction with lipid bilayer environment. The dynamics in turn perturbed insertion. To study this mechanism, a number of experimental studies have used series model peptides (WALP) which consist sequences alternating alanine leucine amino acids terminated pair tryptophans at both ends. It has been shown that, due to hydrophobic mismatch, these can assume tilted conformations respect normal also perturb thickness. In an attempt...

The fusion between two lipid bilayers involves crossing a complicated energy landscape. limiting barrier in the process appears to be closely opposed and intermediate state where outer leaflets are fused. We have performed molecular dynamics simulations characterize free for of liposomes examine details crossing. To capture slow fusion, model using coarse-grained representations lipids was used. pairs simulated four systems: DPPC, DOPC, 3:1 mixture DPPC/DPPE, an asymmetric tail system which...

Significance Wilson disease (WD) is a disorder of copper overload whose variable presentation poses diagnostic and treatment challenges. WD caused by mutations in ATP7B, transporter that loads Cu(I) onto newly synthesized cupro-enzymes the trans -Golgi network (TGN) exports excess trafficking from TGN to plasma membrane. This multidisciplinary study established patient mutation, ATP7B-S653Y, has transport activity TGN, but completely disrupts Cu(I)-responsive trafficking. ATP7B-S653Y...

Background To address the obesity epidemic, there is a need for novel paradigms, including those that timing of eating and sleep in relation to circadian rhythms. Electronic health records (EHRs) are an efficient way identify potentially eligible participants research studies. Mobile (mHealth) apps offer available convenient data collection behaviors, such as sleep. Objective The aim this descriptive analysis was report on recruitment, retention, app use from 6-month cohort study using...