Abstracts of Articles in 1980


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  1. Efficient Trajectory Simulation Methods for Diffusional Barrier Crossing Processes.
  2. Simulation Methods for Protein Structure Fluctuations.
  3. Internal Dynamics of Proteins: Short Time and Long Time Motions of Aromatic Sidechains in PTI.
  4. Molecular Dynamics Studies of NMR Relaxation in Proteins.
  5. Simulation of Protein Dynamics.
  6. Dynamics of Tyrosine Ring Rotations in a Globular Protein.
  7. Molecular Dynamics of Ferrocytochrome c.
  8. Internal Dynamics of Proteins: Short Time and Long Time Motions of Aromatic Sidechains in PTI.
  9. Molecular Dynamics Studies of NMR Relaxation in Proteins.
  10. Helix-Coil Transitions in a Simple Polypeptide Model.
  11. Diffusional Correlations in Polymer Dynamics.
  12. Internal Mobility of Ferrocytochrome c.

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Efficient Trajectory Simulation Methods for Diffusional Barrier Crossing Processes.

Scott H. Northrup and J. Andrew McCammon

Journal of Chemical Physics, Vol. 72, Issue 8, pp. 4569-4578 (1980)

The kinetics of many chemical and biochemical processes in solution are governed by the rate at which systems diffuse across energy barriers separating reactant and product states. These rates can be determined by computer simulation of diffusional trajectories by Brownian dynamics techniques. Conventional simulations, in which systems are dynamically unconstrained, sample barrier crossing events inefficiently since the system spends most of its time in low-energy configurations. New techniques, termed activated and branching-activated trajectory methods, are explored which circumvent this problem by constraining trajectories to the barrier top region. The accuracy and efficiency of these new methods are tested by application to a one-dimensional model chemical system. Activated and branching-activated results for the rate constant are found to converge 10 to 25 times more rapidly than the conventional first passage time method, even for a modest barrier height of 2kBT. Application to more realistic multidimensional systems is discussed in an appendix.


Simulation Methods for Protein Structure Fluctuations.

Scott H. Northrup and J. Andrew McCammon

Biopolymers, Vol. 19, Issue 5, pp. 1001-1016 (1980)

[PubMed: 7378544]

Three numerical techniques for generating thermally accessible configurations of globular proteins are considered; these techniques are the molecular dynamics method, the Metropolis Monte Carlo method, and a modified Monte Carlo method which takes account of the forces acting on the protein atoms. The molecular dynamics method is shown to be more efficient than either of the Monte Carlo methods. Because it may be necessary to use Monte Carlo methods in certain important types of sampling problems, the behavior of these methods is examined in some detail. It is found that an acceptance ratio close to 1/6 yields optimum efficiency for the Metropolis method, in contrast to what is often assumed. This result, together with the overall inefficiency of the Monte Carlo methods, appears to arise from the anisotropic forces acting on the protein atoms due to their covalent bonding. Possible ways of improving the Monte Carlo methods are suggested.


Internal Dynamics of Proteins: Short Time and Long Time Motions of Aromatic Sidechains in PTI.

Martin Karplus, Bruce R. Gelin and J. Andrew McCammon

Biophysical Journal, Vol. 32, Issue 1, pp. 603-618 (1980)

[PubMed: 7248464]

Theoretical approaches to the internal dynamics of proteins are outlined and illustrated by application to the aromatic sidechain motions of tyrosines in the bovine pancreatic trypsin inhibitor. High frequency torsional oscillations are obtained from a molecular dynamics simulation, while the longer time ring rotations are analyzed by use of adiabatic energy minimization and special transition-state trajectory techniques.


Molecular Dynamics Studies of NMR Relaxation in Proteins.

Ronald M. Levy, Martin Karplus and J. Andrew McCammon

Biophysical Journal, Vol. 32, Issue 1, pp. 628-630 (1980)

[PubMed: 19431400]

There is a growing awareness that the visualization of proteins as large rigid molecules, each of which can be described by a single static structure, is inadequate. Instead, it is now realized that proteins undergo structural fluctuations which span a range of times from subpicoseconds to milliseconds or longer. In this report we are concerned with the relation between protein fluctuations occurring on the picosecond to nanosecond time scale and nuclear magnetic resonance (NMR) relaxation experiments.


Simulation of Protein Dynamics.

J.A. McCammon and M. Karplus

Annual Review of Physical Chemistry, Vol. 31, No. 1, pp. 29-45 (1980, Invited review)

Globular proteins exhibit a great variety of internal motions. One indication of this diversity is the range of characteristic times involved, which extends from 10-14s for local vibrations to more than 102s for certain structural transitions. Despite the obvious difficulties in dealing with such complicated systems, the dynamical richness of proteins and the functional importance of their internal motions have attracted the interest of an increasing number of physical chemists in recent years. In particular, the experimental literature on protein dynamics has grown quite rapidly. Many different spectroscopic and kinetic techniques have been used to probe protein motions, in part because of the wide range of time scales involved. Several reviews of this work are now available.


Dynamics of Tyrosine Ring Rotations in a Globular Protein.

J.A. McCammon and M. Karplus

Biopolymers, Vol. 19, Issue 7, pp. 1375-1405 (1980)

The dynamics of activated rotations of a tyrosine ring inside the bovine pancreatic trypsin inhibitor have been studied by computer simulation. The simulation method consists of two parts. In the first part, typical transition-state configurations of the protein atoms are prepared. In the second part, the classical equations of motion for the protein atoms are solved to yield trajectories which pass through these transition-state configurations. Analysis of the trajectories shows that the ring is driven over the rotational potential barrier by nearly impulsive collisions with atoms of the surrounding protein matrix. The collisions are similar to those that occur while the ring oscillates about its equilibrium orientation. The frequency and strength of the collisions are such that transition-state theory is approximately valid for this simple reaction. The enthalpy of activation is substantially reduced by bond-angle deformations which occur rapidly on the time scale of the barrier crossing. Small, transient packing defects in the protein appear to play a role in initiating the ring rotation.


Molecular Dynamics of Ferrocytochrome c.

Scott H. Northrup, Michael R. Pear, J. Andrew McCammon and Martin Karplus

Nature, Vol. 286, No. 5770, pp. 304-305 (1980)

[PubMed: 6250059]

The cytochromes c function as single-electron carriers in the mitochondrial electron transport chain. The native structures of the proteins from different species are quite similar, as are the structures of the reduced and oxidized forms. The 103-residue polypeptide chain of tuna cytochrome c contains 5 alpha-helical segments (residues 2--13, 50--54, 61--69, 71--74, 89--100); the haem group is almost completely buried in a hydrophobic pocket and is covalently bonded to the polypeptide chain by thioether linkages involving Cys 14 and Cys 17 and by linkages to the iron involving His 18 and Met 80. NMR and hydrogen exchange studies indicate significant internal mobility in cytochrome c. In spite of the apparent similarity of the time-average structures of the reduced and oxidized proteins, the structural fluctuations are significantly larger in the latter form. It has been suggested that the internal motions have a role in the electron transfer mechanism. A 16-ps computer simulation of the atomic motions in reduced tuna cytochrome c has now been completed; this reveals various correlations between the magnitudes of the atomic position fluctuations and the structural features of the protein.


Internal Dynamics of Proteins: Short Time and Long Time Motions of Aromatic Sidechains in PTI.

M. Karplus, B.R. Gelin and J.A. McCammon

In "Proteins and Nucleoproteins: Structure, Dynamics and Assembly," V.A. Parsegian, Ed., Rockefeller University Press, New York, N.Y., pp. 603-618 (1980)

Theoretical approaches to the internal dynamics of proteins are outlined and illustrated by application to the aromatic sidechain motions of tyrosines in the bovine pancreatic trypsin inhibitor. High frequency torsional oscillations are obtained from a molecular dynamics simulation, while the longer time ring rotations are analyzed by use of adiabatic energy minimization and special transition-state trajectory techniques.


Molecular Dynamics Studies of NMR Relaxation in Proteins.

R.M. Levy, M. Karplus and J.A. McCammon

In "Proteins and Nucleoproteins: Structure, Dynamics and Assembly," V.A. Parsegian, Ed., Rockefeller University Press, New York, N.Y., pp. 628-629 (1980)

There is a growing awareness that the visualization of proteins as large rigid molecules, each of which can be described by a single static structure, is inadequate. Instead, it is now realized that proteins undergo structural fluctuations which span a range of times from subpicoseconds to milliseconds or longer. In this report we are concerned with the relation between protein fluctuations occurring on the picosecond to nanosecond time scale and nuclear magnetic resonance (NMR) relaxation experiments.


Helix-Coil Transitions in a Simple Polypeptide Model.

J.A. McCammon, S.H. Northrup, M. Karplus and R.M. Levy

Biopolymers, Vol. 19, Issue 11, pp. 2033-2045 (1980)

A simplified model of a polypeptide chain is described. Each residue is represented by a single interaction center. The energy of the chain and the force acting on each residue are given as a function of the residue coordinates. Terms to approximate the effect of solvent and the stabilization energy of helix formation are included. The model is used to study equilibrium and dynamical aspects of the helix-coil transition. The equilibrium properties examined include helix-coil equilibrium constants and their dependence on chain position. Dynamical properties are examined by a stochastic simulation of the Brownian motion of the chain in its solvent surroundings. Correlations in the motions of the residues are found to have an important influence on the helix-coil transition rates.


Diffusional Correlations in Polymer Dynamics.

M.R. Pear, S.H. Northrup and J.A. McCammon

Journal of Chemical Physics, Vol. 73, Issue 9, pp. 4703-4704 (1980)

The authors present a simple theory which shows how viscous forces influence the character of conformational transitions in a polymer.


Internal Mobility of Ferrocytochrome c.

Scott H. Northrup, Michael R. Pear, J. Andrew McCammon, Martin Karplus and Tsunehiro Takano

Nature, Vol. 287, No. 5783, pp. 659-660 (1980)

[PubMed: 6253809]

In the refinement of the X-ray diffraction structures of molecules, it is conventional to introduce atomic 'temperature factors' of the Debye-Waller form to characterize the widths of the electron density peaks corresponding to the atoms. Although these factors are known to include a variety of contributions other than thermal fluctuations of the atomic positions, recent progress in the refinement of protein structures has led to inferences concerning atomic mobilities from the temperature factor data for several proteins. Atomic position fluctuations can be calculated independently by the molecular dynamics method, in which the classical equations of motion for the atoms of an equilibrated protein are solved on a computer. We now show that the X-ray diffraction and dynamical simulation methods yield similar pictures of the atomic mobility in tuna ferrocytochrome c.


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