A General Approach to the Optimization of the Conformation of Ring Molecules with an Application to Valinomycin

Lavery, Richard; Parker, I. D.; Kendrick, John

doi:10.1080/07391102.1986.10506361

Cited by 80 publications

(40 citation statements)

References 19 publications

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“…All of the conformational energy calculations presently described were carried out by using the FLEX parameterization (6,7) developed over several years in our laboratory and already exploited in a large number of studies of nucleic acids and other biological molecules (see, for example, refs. [8][9][10] The first term ofthis formula represents the electrostatic energy, calculated as a sum of interactions between atomic monopoles Q,, obtained from a specially reparameterized Huckel-Del Re procedure (11,12) and damped by a dielectric function E(R) having a sigmoidal form, based on that developed by Hingerty et al (13).…”

Section: Methodsmentioning

confidence: 99%

Energetic coupling between DNA bending and base pair opening.

Ramstein

Lavery

1988

Proc. Natl. Acad. Sci. U.S.A.

307

222

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The pathway for base pair opening within a B-DNA duplex is investigated by theoretical molecular modeling. The results show that the disruption of a single base pair is energetically compatible with the deductions made from hydrogen exchange measurements. In addition, it is found that the opening process is greatly facilitated by DNA bending and that, conversely, once a base pair is disrupted, DNA can bend very easily. It appears that the energetic coupling between these two processes may play an important role in many biological reactions involving nucleic acid distortion. Despite the accumulation of a wealth of information leading to a better knowledge of the chemical mechanism and of the corresponding time range (1-4), the conformational and energetic details of the pathway for opening and the effect of changes in the tertiary structure of DNA remain unclear. Most notably, the mechanism by which a given base pair manages to accumulate enough energy to spontaneously open and disrupt its hydrogen bonds is still fully unknown. These questions are addressed here by theoretical calculations on a B-DNA oligomer. Using the JUMNA (junction minimization of nucleic acids) molecular modeling program (5), we study the energetics and the conformational route for opening one base within a short DNA fragment and then demonstrate how base pair opening and bending of the DNA double helix are related to one another. METHODSAll of the conformational energy calculations presently described were carried out by using the FLEX parameterization (6, 7) developed over several years in our laboratory and already exploited in a large number of studies of nucleic acids and other biological molecules (see, for example, refs. 8-10). The calculations described here were performed under dielectric damping conditions corresponding to aqueous solution (S = 0.16, D = 78). The next three energy terms represent dispersion-repulsion interactions calculated with a 6-12 dependence using, in part, the parameter set developed by Zhurkin et al. (14). Hydrogen bonds (HB) are dealt with by the latter two of these terms, which take into account their angular dependence. All of these terms are summed over pairs of atoms separated by at least three chemical bonds.The last two terms represent the distortion energy associated with torsion angles T, (including anomeric effects) and valence angles a,-To study the base-opening or bending processes within a DNA fragment it is necessary to have control over the helicoidal parameters describing the position of the bases in space as well as parameters indicating the path of the helical axis so that a given "open" or "bent" state can be maintained while energy optimizing the rest of the DNA conformation. This possibility, which is unavailable in normal molecular mechanics procedures, can be achieved with the recently developed JUMNA procedure (5).The aim of the JUMNA approach is to combine the control over the helicoidal parameters of DNA with the rapidity and ease of treating internal conformation changes, i...

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Section: Methodsmentioning

confidence: 99%

Energetic coupling between DNA bending and base pair opening.

Ramstein

Lavery

1988

Proc. Natl. Acad. Sci. U.S.A.

307

222

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“…LIGAND grew out of earlier developments at the Laboratoire de Biochimie Théorique, notably the programs CINFLEX 20 and JUMNA. 21 It is distinct from these two approaches by respectively using a simple minimizer rather than a constrained minimizer and by using pure internal coordinates, rather than a hybrid internal/helicoidal representation.…”

Section: Ligandmentioning

confidence: 99%

“…Any other atoms linked to these main chain atoms are moved in a coupled way by half the rotation that is applied to the moving main chain atoms. 20 Intracyclic valence angles are also variable within the proline ring. This ring is rendered flexible by cutting the C␦ON bond (which is reestablished using a quadratic distance restraint) and treating the C␣-C␦ chain as a linear system.…”

Section: Ligandmentioning

confidence: 99%

“…This is an important problem because there is both experimental and theoretical evidence that multidomain proteins are not rigidly packed, but are rather dynamic structures. 42,43 For these initial tests, we use a helical-hairpin model derived from the PDB entry 1ABZ 44 and consisting of two ␣-helices (residues 6 -16 and 22-33) connected by a loop (residues [17][18][19][20][21]. This system contains 399 atoms and has 242 internal coordinates.…”

Section: Two-domain Protein Modelmentioning

confidence: 99%

“…Energy calculations can be carried out with either our in-house FLEX force field 20 or the AMBER force field 26,27 using the parm98 parameter set. 28 Solvent electrostatic damping can be treated using a dielectric constant, a sigmoidal distance-dependent dielectric function, 21,29 or with the continuum solvent generalized Born (GB) approach using the Tsui and Case parameter set.…”

Section: Ligandmentioning

confidence: 99%

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ARTIST: An activated method in internal coordinate space for sampling protein energy landscapes

et al. 2006

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We present the first applications of an activated method in internal coordinate space for sampling all-atom protein conformations, the activation-relaxation technique for internal coordinate space trajectories (ARTIST). This method differs from all previous internal coordinate-based studies aimed at folding or refining protein structures in that conformational changes result from identifying and crossing well-defined saddle points connecting energy minima. Our simulations of four model proteins containing between 4 and 47 amino acids indicate that this method is efficient for exploring conformational space in both sparsely and densely packed environments, and offers new perspectives for applications ranging from computeraided drug design to supramolecular assembly. Proteins 2006;63:967-975.

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Calculation and analysis of low frequency normal modes for DNA

Ha-Duong

Zakrzewska

1997

J. Comput. Chem.

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A General Approach to the Optimization of the Conformation of Ring Molecules with an Application to Valinomycin

Cited by 80 publications

References 19 publications

Energetic coupling between DNA bending and base pair opening.

Energetic coupling between DNA bending and base pair opening.

ARTIST: An activated method in internal coordinate space for sampling protein energy landscapes

Calculation and analysis of low frequency normal modes for DNA

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