Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “dynamics”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 307 records · Page 17Linked to original sources
PubMed1999

Molecular dynamics simulations of human alpha-lactalbumin: changes to the structural and dynamical properties of the protein at low pH.

Two 700-ps molecular dynamics simulations of human alpha-lactalbumin have been compared. Both were initiated from an X-ray structure determined at pH 6.5. One simulation was designed to represent native conditions and the other the protein in solution at pH 2.0 without a bound calcium ion. The low pH conditions were modelled by protonating the aspartate, glutamate, and histidine side chains and the protein C-terminus. Significant changes were observed for the C-terminal region of the sequence in the simulation at low pH. Most notably an alpha-helix, helix D, and the C-terminal 3(10) helix were substantially disrupted relative to the simulation at high pH. These perturbations to the native fold are similar to those observed in an X-ray structure of alpha-lactalbumin at pH 4.2. In addition, larger fluctuations about side chain torsion angles were observed in the low pH simulation than in that corresponding to the higher pH. These structural and dynamical changes might be representative of the early stages of the transition to the molten-globule state of the protein known to be formed under low pH conditions in solution.

Humans↗
PubMed1999

Structure and dynamics of alpha-MSH using DRISM integral equation theory and stochastic dynamics.

The structural and dynamical features of the hormone alpha-MSH in solution have been examined over a 100 ns time scale by using free energy molecular mechanics models at room temperature. The free energy surface has been modeled using methods from integral equation theory and the dynamics by the Langevin equation. A modification of the accessible surface area friction drag model was used to calculate the atomic friction coefficients. The molecule shows a stable beta-turn conformation in the message region and a close interaction between the side chains of His6, Phe7, and Trp9. A salt bridge between Glu5 and Arg8 was found not to be a preferred interaction, whereas a Glu5 and Lys11 salt bridge was not sampled, presumably due to relatively high free energy barriers. The message region was more conformationally rigid than the N-terminal region. Several structural features observed here agree well with experimental results. The conformational features suggest a receptor-hormone interaction model where the hydrophobic side chains of Phe7 and Trp9 interact with the transmembrane portion of the MC1 receptor. Also, the positively charged side chain of Arg8 and the imidazole side chain of His6 may interact with the negatively charged portions of the receptor which may even be on the receptor's extracellular loops.

Algorithms↗
PubMed2001

Dynamic deconvolution of a pre-equilibrated dynamic combinatorial library of acetylcholinesterase inhibitors.

A dynamic combinatorial library composed of interconverting acylhydrazones has been generated and screened towards inhibition of acetylcholinesterase from the electric ray Torpedo marmorata. Starting from a small set (13) of initial hydrazide and aldehyde building blocks, a library containing possibly 66 different species was obtained in a single operation. Of all possible acylhydrazones formed, active compounds containing two terminal cationic recognition groups separated by an appropriate distance, permitting two-site binding, could be rapidly identified by using a dynamic deconvolution--screening procedure, based on the sequential removal of starting building blocks. A very potent bis-pyridinium inhibitor (K(i)=1.09 nM, alphaK(i)=2.80 nM) was selected from the process and the contribution of various structural features to inhibitory potency was evaluated.

Acetylcholinesterase↗
PubMed2004

Dynamics of water molecules buried in cavities of apolipoprotein E studied by molecular dynamics simulations and continuum electrostatic calculations.

Molecular dynamics (MD) simulations of several nanoseconds each were used to monitor the dynamic behavior of the five crystal water molecules buried in the interior of the N-terminal domain of apolipoprotein E. These crystal water molecules are fairly well conserved in several apolipoprotein E structures, suggesting that they are not an artifact of the crystal and that they may have a structural and/or functional role for the protein. All five buried crystal water molecules leave the protein interior in the course of the longest simulations and exchange with water molecules from the bulk. The free energies of binding evaluated from the electrostatic binding free energy computed using a continuum model and estimates of the binding entropy changes represent shallow minima. The corresponding calculated residence times of the buried water molecules range from tens of picoseconds to hundreds of nanoseconds, which denote rather short times as for buried water molecules. Several water exchanges monitored in the simulations show that water molecules along the exit/entrance pathway use a relay of H bonds primarily formed with charged residues which helps either the exit or the entrance from or into the buried site. The exit/entrance of water molecules from/into the sites is permitted essentially by local motions of, at most, two side chains, indicating that, in these cases, complex correlated atomic motions are not needed to open the buried site toward the surface of the protein. This provides a possible explanation for the short residence times.

Apolipoproteins E↗
PubMed2006

The trans-cis isomerization reaction dynamics in sensory rhodopsin II by femtosecond time-resolved midinfrared spectroscopy: chromophore and protein dynamics.

Transient infrared (IR) vibrational spectroscopy at subpicosecond time resolution on sensory rhodopsin II from Natronomonas pharaonis, NpSRII, has been performed for the first time. The experiments yield three time constants for the description of the primary photoinduced reaction dynamics, i.e. 0.5, 3.7-4.4, and 11 ps. The data are consistent with a sequential reaction scheme, with the isomerization taking place within 0.5 ps, succeeded by an electronic ground state relaxation. The 11 ps component, observed at 1550 and 1530 cm(-1), is attributed to dynamics of protein vibrational bands, possibly amide II bands of the protein backbone, perturbed by the ultrafast retinal photoisomerization. Similar observations, yet not as strongly expressed, have been made earlier in bacteriorhodopsin and halorhodopsin.

Bacteriorhodopsins↗
PubMed1990

Dynamic properties of the first enzymatic reaction steps of porcine pancreatic elastase. How rigid is the active site of the native enzyme? Molecular dynamics simulation.

Two molecular dynamics simulations (100 and 50 ps) of native porcine pancreatic elastase i.e., without bound substrate and with the active site hydrated by a dome of water (630 molecules) have been performed. Dynamical properties of the catalytic tetrad have been examined. While relative conformations of the Asp 102, His 57, and Ser 214 are rather stable in time, the side chain of Ser 195 undergoes several conformational changes. No preferences are observed for the formation of a hydrogen bond between the O gamma-H group (Ser 195) and nitrogen N, (His 57). A cluster of ordered water molecules effectively competes with the H-O gamma group (Ser 195) and thereby prevents the formation of this H bond, which is generally agreed to be crucial for catalysis.

Animals↗
PubMed2003

Electron transfer and dynamic infrared-band coalescence: it looks like dynamic NMR spectroscopy, but a billion times faster.

Broadening and coalescence of infrared bands can occur due to chemical exchange processes occurring on very fast, femtosecond-to-picosecond timescales. One such fast process of recent investigation is intramolecular electron transfer in transition-metal complexes with strong communication between electron-donor and -acceptor sites. The observation of partial coalescence of metal-carbonyl stretching bands in hexanuclear ruthenium mixed-valence complexes due to electron-transfer rates on the order of 10(11)-10(12) s(-1) is chronicled here. Several important advances have been made with the aid of dynamic infrared-band coalescence in these complexes, including the observation of dynamic solvent relaxation effects on electron-transfer rates, the determination of the equilibrium constant between charge-transfer isomers, and a reconsideration of the theory of electron transfer and delocalization in bridged, near-delocalized electron-transfer systems.

Journal Article↗
PubMed2007

Molecular dynamics study of the conformational dynamics and energetics of some large-ring cyclodextrins (CDn, n = 24, 25, 26, 27, 28, 29).

Molecular dynamics simulations in water solution were performed on six large-ring cyclodextrins (LR-CDs) with a degree of polymerization 24, 25, 26, 27, 28, and 29. The AMBER parm99 force field and explicit water molecules (TIP3P) were used in the simulations. The present research was aimed at further extending our knowledge on the structural dynamics and the energetics of this new class of compounds that may eventually provide chiral cavities suitable for formation of inclusion complexes with small molecules, and, accordingly, to serve as host structures for chiral recognition. The study focused on several representatives flanking CD26-the largest LR-CD for which X-ray data is available. Both the monitoring of the structural variations during the simulations as well as the analyses of energy balances are indicative for high flexibility of the macrorings. Slight differences of the overall preferred shapes were detected with diminishing the size of the macromolecules from CD29 to CD24. An elongated cavity (CD28) or a double parallel strand in different specific representations are the dominating motifs in the LR-CDs studied: with loops at the two ends (CD25, CD28, CD29), with a loop at one end (CD25), twisted (CD26, CD27) or twisted with an open portion in the middle (CD24), helical (CD24, CD25), or linking two loops from one of their sides (CD27). Two loops connected by an arc (CD28, CD29) and a cavity with the shape of an extended rectangular (CD24, CD28) appear preferentially during the conformational interconversions of the two larger CDs, whereas helical motifs are present in the smaller macrorings: an extended helix with ends linked by an arc (CD24), helical turn and helical portion (CD26, CD27). A triple propeller conformation or three symmetrical loops of almost equal size were also detected for CD26 and CD29, respectively. The present results further support the hypothesis for the existence of more than one cavity in large-ring cyclodextrins and suggest preferred conformations in water solution for the LR-CDs with degree of polymerization from 24 to 29.

Journal Article↗
PubMed2007

Protein dynamics tightly connected to the dynamics of surrounding and internal water molecules.

Proteins are key components of biological cells. For example, enzymes catalyze biochemical reactions, membrane transporters are responsible for uptake and release of critical and superfluous components from the cell environment, and structural proteins are responsible for the stability of the cell wall and cytoskeleton. Many of the diverse protein functions involve dynamic transitions ranging from small local atomic displacements up to large allosteric conformational changes. In any conformation, proteins are in contact with the universal solvent medium of cells, water. Water not only surrounds proteins but is often an integral part of proteins and also is involved in key mechanistic steps. This Minireview discusses recent experimental and theoretical results on the role of water for protein dynamics and function.

Hydrogen Bonding↗
PubMed2004

Structure and dynamics of the CrIII ion in aqueous solution: Ab initio QM/MM molecular dynamics simulation.

Structural and dynamical properties of the Cr(III) ion in aqueous solution have been investigated using a combined ab initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics simulation. The hydration structure of Cr(III) was determined in terms of radial distribution functions, coordination numbers, and angular distributions. The QM/MM simulation gives coordination numbers of 6 and 15.4 for the first and second hydration shell, respectively. The first hydration shell is kinetically very inert but by no means rigid and variations of the first hydration shell geometry lead to distinct splitting in the vibrational spectra of Cr(H(2)O)(6) (3+). A mean residence time of 22 ps was obtained for water ligands residing in the second hydration shell, which is remarkably shorter than the experimentally estimated value. The hydration energy of -1108 +/- 7 kcal/mol, obtained from the QM/MM simulation, corresponds well to the experimental hydration enthalpy value.

Journal Article↗
PubMed2005

Structure and dynamics of hydrated NH(4) (+): an ab initio QM/MM molecular dynamics simulation.

A combined ab initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics simulation has been performed to investigate solvation structure and dynamics of NH(4) (+) in water. The most interesting region, the sphere includes an ammonium ion and its first hydration shell, was treated at the Hartree-Fock level using DZV basis set, while the rest of the system was described by classical pair potentials. On the basis of detailed QM/MM simulation results, the solvation structure of NH(4) (+) is rather flexible, in which many water molecules are cooperatively involved in the solvation shell of the ion. Of particular interest, the QM/MM results show fast translation and rotation of NH(4) (+) in water. This phenomenon has resulted from multiple coordination, which drives the NH(4) (+) to translate and rotate quite freely within its surrounding water molecules. In addition, a "structure-breaking" behavior of the NH(4) (+) is well reflected by the detailed analysis on the water exchange process and the mean residence times of water molecules surrounding the ion.

Journal Article↗
PubMedDate not supplied

Solitary hepatic metastasis: comparison of dynamic contrast-enhanced CT and MR imaging with fat-suppressed T2-weighted, breath-hold T1-weighted FLASH, and dynamic gadolinium-enhanced FLASH sequences.

Twenty consecutive cancer patients with a solitary hepatic metastasis detected with dynamic contrast-material-enhanced computed tomography (CT) who were considered for hepatic resection underwent magnetic resonance (MR) imaging within 18 days after CT. Histologic confirmation was obtained in all lesions. CT depicted 20 solitary lesions. MR imaging showed a solitary lesion in 14 patients, two lesions in three patients, and more than two lesions in three patients, for a total of 37 lesions. Twenty-three lesions less than 2 cm in diameter were missed with CT, and six lesions less than 1.3 cm in diameter were missed with MR imaging. MR imaging was superior to CT in the detection of hepatic metastases on a patient-by-patient basis (P < .01). The results suggest that MR imaging is superior to dynamic contrast-enhanced CT for the detection of hepatic metastases.

Colorectal Neoplasms↗
PubMed2005

Study of the Villin headpiece folding dynamics by combining coarse-grained Monte Carlo evolution and all-atom molecular dynamics.

The folding mechanism of the Villin headpiece (HP36) is studied by means of a novel approach which entails an initial coarse-grained Monte Carlo (MC) scheme followed by all-atom molecular dynamics (MD) simulations in explicit solvent. The MC evolution occurs in a simplified free-energy landscape and allows an efficient selection of marginally-compact structures which are taken as viable initial conformations for the MD. The coarse-grained MC structural representation is connected to the one with atomic resolution through a "fine-graining" reconstruction algorithm. This two-stage strategy is used to select and follow the dynamics of seven different unrelated conformations of HP36. In a notable case the MD trajectory rapidly evolves towards the folded state, yielding a typical root-mean-square deviation (RMSD) of the core region of only 2.4 A from the closest NMR model (the typical RMSD over the whole structure being 4.0 A). The analysis of the various MC-MD trajectories provides valuable insight into the details of the folding and mis-folding mechanisms and particularly about the delicate influence of local and nonlocal interactions in steering the folding process.

Algorithms↗
PubMed2006

Structural and dynamical properties of manganese catalase and the synthetic protein DF1 and their implication for reactivity from classical molecular dynamics calculations.

There is a pressing need for accurate force fields to assist in metalloprotein analysis and design. Recent work on the design of mimics of dimetal proteins highlights the requirements for activity. DF1 is a de novo designed protein, which mimics the overall fold and active site geometry of a series of diiron and dimanganese proteins. Specifically, the dimanganese form of DF1 is a mimic of the natural enzyme manganese catalase, which catalyzes the dismutation reaction of hydrogen peroxide into water and oxygen. During catalytic turnover, the active site has to accommodate both the reduced and the oxidized state of the dimanganese core. The biomimetic protein DF1 is only stable in the reduced form and thus not active. Furthermore, the synthetic protein features an additional bridging glutamate sidechain, which occupies the substrate binding site. The goal of this study is to develop classical force fields appropriate for design of such important dimanganese proteins. To this aim, we use a nonbonded model to represent the metal-ligand interactions, which implicitly takes into account charge transfer and local polarization effects between the metal and its ligands. To calibrate this approach, we compare and contrast geometric and dynamical properties of manganese catalase and DF1. Having demonstrated a good correspondence with experimental structural data, we examine the effect of mutating the bridging glutamate to aspartate (M1) and serine (M2). Classical MD based on the refined forcefield shows that these point mutations affect not only the immediate coordination sphere of the manganese ions, but also the relative position of the helices, improving the similarity to Mn-catalase, especially in case of M2. On the basis of these findings, classical molecular dynamics calculations with the active site parameterization scheme introduced herein seem to be a promising addition to the protein design toolbox.

Binding Sites↗
PubMed1995

Structure and internal dynamics of the bovine pancreatic trypsin inhibitor in aqueous solution from long-time molecular dynamics simulations.

Structural and dynamic properties of bovine pancreatic trypsin inhibitor (BPTI) in aqueous solution are investigated using two molecular dynamics (MD) simulations: one of 1.4 ns length and one of 0.8 ns length in which atom-atom distance bounds derived from NMR spectroscopy are included in the potential energy function to make the trajectory satisfy these experimental data more closely. The simulated properties of BPTI are compared with crystal and solution structures of BPTI, and found to be in agreement with the available experimental data. The best agreement with experiment was obtained when atom-atom distance restraints were applied in a time-averaged manner in the simulation. The polypeptide segments found to be most flexible in the MD simulations coincide closely with those showing differences between the crystal and solution structures of BPTI.

Animals↗
PubMed1997

Dynamic Adsorption Behavior of Polyethylene Glycol Octylphenyl Ethers at the Water/Oil Interface Studied by a Dynamic Drop Volume Technique

The dynamic drop volume technique has been used to measure the dynamic interfacial tensions of nonionic surfactants (Triton X-45, X-100, X-165, and X-405) at the water/nonane and water/butylbenzene interface. The measurements were performed under the conditions of equilibrium distribution of the surfactant between the two liquid phases established after a sufficiently high number of aqueous solution drops have been formed within a small volume of the oil phase under study. The diffusion kinetics model for the description of the adsorption at the surface of growing drops involves equilibrium surfactant distribution and adsorption from both adjacent phases. Two orientational states of adsorbed surfactant molecule at the interface were assumed in agreement with recently published results at the water/air interface. Good agreement between this theory and the experimental data was obtained.

Journal Article↗
PubMed1993

Molecular dynamics with weighted time-averaged restraints for a DNA octamer. Dynamic interpretation of nuclear magnetic resonance data.

For conformationally flexible molecules in solution, NMR-derived distance restraints are time-averaged. In contrast to deriving structures from NMR distance constraints via conventional restrained molecular dynamics (rMD), the range of conformational flexibility may be better represented by MD simulations using weighted time-averaged restrains (MD-tar). This approach has been utilized for dynamic structure refinement of the DNA octamer [d(GTATAATG].[d(CATATTAC)] which contains the Pribnow box consensus sequence. An improved set of distance restraints was calculated via complete relaxation matrix analysis utilizing the solution structure of the octamer which was determined previously by rMD as a starting model. MD-tar calculations were performed with the program AMBER4 under various conditions, some including explicit solvent. All trajectories generated via MD-tar exhibited reduced constraint energies and average deviations for the distances compared to standard rMD. Quantitative comparison with experimental data, i.e. two-dimensional NOE intensities and COSY-derived coupling constants yielded a significant improvement for MD-tar simulated structures relative to rMD-derived structures. The conformational envelope of the MD-tar structures is wider than that from rMD and even unrestrained MD. Explicit solvent force-fields tightened the conformational envelope, leading to even better agreement with experimental data. All MD-tar simulations exhibit sugar repuckering for basically all residues, yielding a minor population in the low N-region and one or more S-conformers. For most backbone torsion angles, one or more minor conformers were found, while the major conformations generally coincided with those obtained in standard rMD. Distributions of helical parameters for MD-tar trajectories are rather symmetric but slightly broader than those for rMD. Average values and associated standard deviations are discussed with respect to sequence-dependent variations. All trajectories obtained with an explicit solvent force field exhibited a narrower minor groove compared to in vacuo calculations.

Carbohydrate Conformation↗
PubMed1995

Structure, dynamics and energetics of initiation sites in protein folding: I. Analysis of a 1 ns molecular dynamics trajectory of an early folding unit in water: the helix I/loop I-fragment of barnase.

The dynamic and energetic behavior of an initiation site of protein folding (helix I/loop I fragment of barnase) isolated from the tertiary environment of the rest protein is investigated in a 1 ns molecular dynamics simulation. All atom representation, explicit solvent description, and periodic boundary conditions are applied. In the course of the simulation several steps of structural disintegration are observed, followed by events partially rebuilding the initial structure. The phase of disintegration results in a fragment conformation completely lacking hydrogen bonds, with one residue in the center of the helix changed from alpha to beta conformation. The transition state of helix disintegration is characterized by a complete i-->i + 4/i + 5 hydrogen bonding network which undergoes gradual hydrolysis starting at the solvent exposed flank and proceeding towards the interior of the fragment perpendicular to the axis of the helix. Energetic analysis of the helix transitions shows that the i-->i + 4/i-->i + 5 network of hydrogen bonds accommodates one helical residue in beta conformation with only slightly worse hydrogen bonding energy and Van der Waals packing compared to the regular alpha-helix. The stability of the fragment is primarily due to hydrophobic interactions of residues shown to be essential in mutagenesis experiments.

Amino Acid Sequence↗