An ad hoc method for calculating the entropy of a biomolecular system from covariance matrix atomic fluctuations is analyzed. It shown that its essential assumption can be eliminated by quasiharmonic analysis. The computer time required use latter same order as former.

The microscopic details of how peptides translocate one at a time through nanopores are crucial determinants for transport membrane pores and important in developing nano-technologies. To date, the translocation process has been too fast relative to resolution single molecule techniques that sought detect its milestones. Using pH-tuned single-molecule electrophysiology molecular dynamics simulations, we demonstrate peptide passage α-hemolysin protein can be sufficiently slowed down observe...

The ability to modulate alignment and measure multiple independent sets of NMR residual dipolar couplings (RDCs) has made it possible characterize internal motions in proteins at atomic resolution with time scale sensitivity ranging from picoseconds up milliseconds. application such methods the study RNA dynamics, however, remains fundamentally limited by inability strong between overall that complicate quantitative interpretation RDCs. Here, we address this problem showing can be generally...

Significance The novel coronavirus (SARS-CoV-2) pandemic resulted in the largest public health crisis recent times. Significant drug design effort against SARS-CoV-2 is focused on receptor-binding domain (RBD) of spike protein, although this region highly prone to mutations causing therapeutic resistance. We applied deep data analysis methods all-atom molecular dynamics simulations identify key non-RBD residues that play a crucial role spike−receptor binding and infection. Because are...

A Monte Carlo simulated annealing algorithm based on the generalized entropy of Tsallis is presented. The obeys detailed balance and reduces to a steepest descent at low temperatures. Application conformational optimization tetrapeptide demonstrates that more effective in locating energy minima than standard molecular dynamics or methods.

We describe a strategy for constructing atomic resolution dynamical ensembles of RNA molecules, spanning up to millisecond timescales, that combines molecular dynamics (MD) simulations with NMR residual dipolar couplings (RDC) measured in elongated RNA. The are generated via Monte Carlo procedure by selecting snap-shot from an MD trajectory reproduce experimentally RDCs. Using this approach, we construct two variants the transactivation response element (TAR) containing three (HIV-1) and...

Significance The virus bacteriophage T4 infects the bacterium Escherichia coli using an intriguing nanoscale injection machinery that employs a contractile tail. is responsible for recognizing and puncturing bacterial host transferring viral genome into during infection. Fundamental questions remain concerning how this process unfolds in real time, presently defies direct experimental observation. Using combination of atomistic continuum representations, study contributes system-level model...

Generalized Monte Carlo and molecular dynamics algorithms which provide enhanced sampling of the phase space in calculation equilibrium thermodynamic properties is presented. The algorithm samples trial moves from a generalized statistical distribution derived modification Gibbs–Shannon entropy proposed by Tsallis. Results for one-dimensional model potential demonstrate that leads to greatly rate barrier crossing convergence averages. Comparison made with standard Metropolis J-walking Franz,...

The molecular structures and enthalpy release of poly(amidoamine) (PAMAM) dendrimers binding to 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers were explored through atomistic dynamics. Three PAMAM dendrimer terminations examined: protonated primary amine, neutral acetamide, deprotonated carboxylic acid. Fluid gel lipid phases examined extract the effects tail mobility on generation-3 dendrimers, which are directly relevant nanoparticle interactions involving rafts, endocytosis,...

Dynamic disorder in proteins, as demonstrated by variations single-molecule electron transfer rates, is investigated molecular dynamics simulations. The potential of mean force for the fluctuating donor−acceptor distance calculated NAD(P)H:flavin oxidoreductase (Fre) complex with flavin adenine dinucleotide (FAD) and found to be agreement that estimated from experiments. autocorrelation function fluctuations has a simple exponential behavior at low temperatures stretched higher on...

Third-generation (G3) poly(amidoamine) (PAMAM) dendrimers are simulated approaching 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers with fully atomistic molecular dynamics, which enables the calculation of a free energy profile along approach coordinate. Three different dendrimer terminations examined: protonated primary amine, uncharged acetamide, and deprotonated carboxylic acid. As lipids become closer, their attractive force increases (up to 240 pN) becomes deformed as it...

Abstract In naked duplex DNA, G–C and A–T Watson-Crick base pairs exist in dynamic equilibrium with their Hoogsteen counterparts. Here, we used nuclear magnetic resonance (NMR) relaxation dispersion molecular dynamics (MD) simulations to examine how Watson-Crick/Hoogsteen are modulated upon recognition of DNA by the bisintercalator echinomycin monointercalator actinomycin D. both cases, results quenching at involved intermolecular base-specific hydrogen bonds. case echinomycin, population...

We introduce a rare-event sampling scheme, named Markovian Weighted Ensemble Milestoning (M-WEM), which inlays weighted ensemble framework within milestoning theory to efficiently calculate thermodynamic and kinetic properties of long-time-scale biomolecular processes from short atomistic molecular dynamics simulations. M-WEM is tested on the Müller-Brown potential model, conformational switching in alanine dipeptide, millisecond time-scale protein-ligand unbinding trypsin-benzamidine...

The “Smart Walking” Monte Carlo algorithm is examined. In general, due to a bias imposed by the interbasin trial move, does not satisfy detailed balance. While it has been shown that can provide good estimates of equilibrium averages for certain potentials, other potentials are poor. A modified version algorithm, Smart Darting Carlo, which obeys balance condition, proposed. Calculations on one-dimensional model potential, Lennard-Jones cluster and alanine dipeptide demonstrate accuracy...

Sequence-specific DNA flexibility plays a key role in variety of cellular interactions that are critical for gene packaging, expression, and regulation, yet few studies have experimentally explored the sequence dependence dynamics occur on biologically relevant time scales. Here, we use nuclear magnetic resonance (NMR) carbon spin relaxation combined with molecular (MD) simulations to examine picosecond nanosecond dinucleotide steps as well varying length homopolymeric An·Tn repeats...

To directly simulate rare events using atomistic molecular dynamics is a significant challenge in computational biophysics. Well-established enhanced-sampling techniques do exist to obtain the thermodynamic functions for such systems. However, developing methods obtaining kinetics of long timescale processes from simulation at atomic detail comparatively less developed an area. Milestoning and weighted ensemble (WE) method are two different stratification strategies; both have shown promise...

The development of methods for predicting NMR chemical shifts with high accuracy and speed is increasingly allowing use these abundant, readily accessible measurements in determining the structure dynamics proteins. For nucleic acids, however, despite availability semiempirical (1)H shifts, their has not yet been examined. Here, we show that offer powerful restraints RNA determination, discrimination native from non-native states to within 2-4 Å, <3 Å when highly flexible residues are...