Time-dependent distance restraints in molecular dynamics simulations

Torda, Andrew E.; Scheek, Ruud M.; Gunsteren, Wilfred F. van

doi:10.1016/0009-2614(89)87249-5

Cited by 268 publications

(222 citation statements)

References 11 publications

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“…In this method the quadraticdistance-restraining potential is replaced by a potential where the instantaneous distance is replaced by an average distance [32]. The exponentially weighted average is controlled by a time constant z, which weights the most recent history most heavily.…”

Section: Methodsmentioning

confidence: 99%

“…After this, the simulation was continued for 20 ps with time-averaged restraints. The simulation was started, as suggested by Torda et al [32], by making all initial average distances 0.02 nm smaller than the target upperbound distance, thus allowing the restraint forces to build up gradually where needed. The memory time constant was taken to be 2.5 ps and the heat-bath-coupling time constant 0.01 ps.…”

Section: Methodsmentioning

confidence: 99%

“…This might indicate local mobility, so that the NOE restraints cannot be satisfied simultaneously. To test this possibility, we also performed a time-averaged RMD simulation [32]. Time-averaged distance restraining allows more mobility in the molecule while keeping the restraints, on average, satisfied during the simulation.…”

Section: Local Mobilitymentioning

confidence: 99%

See 2 more Smart Citations

The solution structure of a monomeric insulin

Knegtel

Boelens

Ganadu

et al. 1991

European Journal of Biochemistry

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The solution conformation of des-(B26-B30)-insulin (DPI) has been investigated by 'H-NMR spectroscopy. A set of 250 approximate interproton distance restraints, derived from two-dimensional nuclear Overhauser enhancement spectra, were used as the basis of a structure determination using distance geometry (DG) and distance-bound driven dynamics (DDD). Sixteen DG structures were optimized using energy minimization (EM) and submitted to short 5-ps restrained molecular dynamics (RMD) simulations. A further refinement of the DDD structure with the lowest distance errors was done by energy minimization, a prolonged RMD simulation in VUL'UO and a time-averaged RMD simulation. An average structure was obtained from a trajectory generated during 20-ps RMD. The final structure was compared with the des-(B26 -B30)-insulin crystal structure refined by molecular dynamics and the 2-Zn crystal structure of porcine insulin. This comparison shows that the overall structure of des-(B26 -B30)-insulin is retained in solution with respect to the crystal structures with a high flexibility at the N-terminal part of the A chain and at the N-terminal and C-terminal parts of the B chain. In the RMD run a high mobility of Gly A l , Asn A21 and of the side chain of Phe B25 is noticed. One of the conformations adopted by des-(B26-B30)-insulin in solution is similar to that of molecule 1 (Chinese nomenclature) in the crystal structure of porcine insulin.Due to its biological importance as a hormone and drug, insulin has been the subject of numerous studies regarding its structure and function [l]. Several crystal structures of insulins have been reported [2 -61 and a detailed picture of the spatial structure of insulins has emerged.The insulin molecule consists of two polypeptide chains, A and B, of 21 and 30 residues respectively (cf. Fig. 1). The horse-shoe-shaped A chain contains two helices (residues A2-A8 and A13-A20) and the B chain one helix (residues B9 -BI 9). These chains are connected by two disulphide bridges (A7 -B7 and A20 -B19) which, together with a third one (A6 -A1 I), help stabilize the folded form of insulin over a broad range of temperatures and pH values. In the crystal structures the last six residues of the B chain form an antiparallel fl-sheet with another insulin molecule. Insulin is a rather flexible molecule, as evidenced by large structural differences found in different crystal structures. The major differences between various forms of insulin are in the N-terminal of the B chain. For instance, the porcine 4-Zn insulin structure has an additional helical region running from B1 to B8 [4], whereas in 2-Zn insulin this fragment is in a random coil conformation. In fact, a variety of solution and crystal studies showed that the conversion of the 2-Zn to the 4-Zn structure can be induced by high concentrations of anions [7]. Adding Correspondence to R . Boelens, Department of Chemistry, University of Utrecht, Padualaan 8, 3584 CH Utrecht, The NetherlandsAhbveviutions. Des-(3326 -B30)-insulin, insulin lacking the C-te...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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The solution structure of a monomeric insulin

Knegtel

Boelens

Ganadu

et al. 1991

European Journal of Biochemistry

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“…To avoid the ester substrate diffusing away from the active site, three pairwise distance restraints (less than 3 Å with the force constant of 50 kcal.mol -1 .Å -2 ) were incorporated during MD simulations, i.e., distance between OG from Ser 146 and C1 from the ester substrate, distance between O1 from the ester substrate and H from Leu 147 and distance between O1 from the ester substrate and H from Ser 83 ( Fig. 1) [29]. The long-range electrostatic interactions were treated using particle mesh…”

Section: Simulationsmentioning

confidence: 99%

New insights into the molecular mechanism of methanol-induced inactivation ofThermomyces lanuginosuslipase: a molecular dynamics simulation study

Tong

Busk

Lange

et al. 2015

Molecular Simulation

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Methanol intolerance of lipase is a major limitation in lipase-catalyzed methanolysis reactions.In this study, to understand the molecular mechanism of methanol-induced inactivation of lipases, we performed molecular dynamics (MD) simulations of Thermomyces lanuginosus lipase (TLL) in water and methanol and compared the observed structural and dynamic properties. The solvent accessibility analysis showed that in methanol, polar residues tended to be buried away from the solvent while non-polar residues tended to be more solventexposed in comparison to those in water. Moreover, we observed that in methanol, the van der Waals packing of the core residues in two hydrophobic regions of TLL became weak.

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“…In addition, omitting the averaging h i r from V qr will strongly reduce the mobility of the molecular system (Torda et al, 1990;Nanzer et al, 1995). A better approach is to approximate the ensemble average AEq(r)ae r by a time (trajectory) average (Torda et al, 1989) or by an average over different molecules Bonvin et al, 1994;Fennen et al, 1995). In MD simulations the use of the time average…”

Section: Introductionmentioning

confidence: 99%

On using oscillating time-dependent restraints in MD simulation

et al. 2006

Self Cite

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The use of time-dependent restraints in molecular simulation in order to generate a conformational ensemble for molecules that is in accordance with measured ensemble averages for particular observable quantities is investigated. Using a model system consisting of liquid butane and the cyclic peptide antamanide the reproduction of particular average 3 J-coupling constant values in a molecular dynamics simulation is analysed. It is shown that the multiple-valuedness and the sizeable gradients of the Karplus curve relating 3

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Time-dependent distance restraints in molecular dynamics simulations

Cited by 268 publications

References 11 publications

The solution structure of a monomeric insulin

The solution structure of a monomeric insulin

New insights into the molecular mechanism of methanol-induced inactivation ofThermomyces lanuginosuslipase: a molecular dynamics simulation study

On using oscillating time-dependent restraints in MD simulation

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