J. Andrew McCammon

The structure of liquid water at an extended hydrophobic surface

Molecular dynamics simulations have been carried out for liquid water between flat hydrophobic surfaces. The surfaces produce density oscillations that extend at least 10 A into the liquid, and significant molecular orientational preferences that extend at least 7 A into the liquid. The liquid structure nearest the surface is characterized by ‘‘dangling’’ hydrogen bonds; i.e., a typical water molecule at the surface has one potentially hydrogen‐bonding group oriented toward the hydrophobic surface. This surface arrangement represents a balance between the tendencies of the liquid to maximize the number of hydrogen bonds on the one hand, and to maximize the packing density of the molecules on the other. A detailed analysis shows that the structural properties of the liquid farther from the surface can be understood as effects imposed by this surface structure. These results show that the hydration structure of large hydrophobic surfaces can be very different from that of small hydrophobic molecules.

Molecular dynamics with stochastic boundary conditions

Abstract We present and illustrate a simple approach for carrying out molecular dynamics simulations subject to stochastic boundary conditions. Methods of this type are expected to be useful in the study of chemical reactions and other localized processes in dense media.

Stochastically gated diffusion‐influenced reactions

The theory of diffusion‐influenced reactions is extended to cases where the reactivity of the species fluctuates in time (e.g., the accessibility of a binding site of a protein is modulated by a gate). The opening and closing of the gate is assumed to be a stationary Markov process [i.e., it is described by the kinetic scheme (open) a⇄b (closed)]. When the reaction is described by suitable boundary conditions, by solving the appropriate reaction‐diffusion equations, it is shown that the stochastically gated association rate constant (kSG) is given by k−1SG=k−1∞ + [a−1 b(a+b)κu(a+b)]−1, where κu(s) is the Laplace transform of the time‐dependent rate constant of the ungated problem and k∞ is the corresponding steady‐state rate constant. The limits when the relaxation time for gate fluctuations is larger or smaller than the characteristic time for diffusion are considered. The relation to previous work is discussed. The theory is applied to three models: (i) a gated sphere, (ii) a gated disk on an infinite...

Sodium chloride ion pair interaction in water: computer simulation

Abstract The thermodynamics and structure of a sodium chloride ion pair in liquid water are studied as a function of the ion pair separation. Distinct minima in the free energy of the system are found for contact and solvent separated ion geometries.

Molecular dynamics of ferrocytochrome c: Magnitude and anisotropy of atomic displacements

Abstract Two computer simulations of the atomic motion in tuna ferrocytochrome c have been carried out. The average structures and the structural correlations of the magnitudes of the atomic position fluctuations are in substantial agreement with recent X-ray diffraction results, particularly for the protein interior. The simulations show, however, that the atomic displacements are quite anisotropic. The degree of anisotropy and the preferred directions of atomic displacement exhibit correlations with structural features of the protein.

Brownian dynamics with rotation–translation coupling

A generalized algorithm is proposed for simulating a system of interacting spherical particles simultaneously executing both rotational and translational Brownian motion. Rotation–translation couplings are obtained numerically for (a) a pair of rigid spheres using the generalized algorithm and (b) a pair of rigid cubic octamer particles using a translational algorithm with rigid constraints. The likely importance of rotation–translation coupling in the Brownian–dynamics context is discussed.

Generalized Langevin dynamics simulations with arbitrary time‐dependent memory kernels

An algorithm is described that allows dynamical simulations to be performed based on generalized Langevin equations with arbitrary, time‐dependent memory kernels. Test simulations show that good results are obtained for kernels with distinctly different forms (e.g., exponential and Gaussian).

Molecular dynamics of phenylalanine transfer RNA.

The atomic motions of yeast phenylalanine transfer RNA have been simulated using the molecular dynamics algorithm. Two simulations were carried out for a period of 12 picoseconds, one with a normal Van der Waals potential and the other with a modified Van der Waals potential intended to mimic the effect of solvent. An analysis of large scale motions, surface exposure, root mean square displacements, helical oscillations and relaxation mechanisms reveals the maintenance of stability in the simulated structures and the general similarity of the various dynamic features of the two simulations. The regions of conformational flexibility and rigidity for tRNA(Phe) have been shown in a quantitative measure through this approach.

Pressure dependence of aromatic ring rotations in proteins: a collisional interpretation

Activated processes are of central importance to many biochemical phenomena, including ligand binding and enzyme catalysis [1,2]. A simple model for such processes, provided by the rotation (flipping) o f aromatic amino acid sidechains in the interior of globular protein has been studied intensively by experimental [3-8] and theoretical techniques [9-12]. Energy minimization [9,10] and activated trajectory [11,12] calculations have demonstrated that the nature of the rotational transition and its effective barrier are determined by the positions and fluctuations of the protein matrix atoms surrounding the aromatic ring. The importance of frictional effects for the ring motion and for other processes involving fluctuations in the protein interior has been pointed out [11-15]. Recently, Wagner [ 16,17] has determined the hydrostatic pressure dependence of the aromatic ring rotation rates in the bovine pancreatic trypsin inhibitor (PTI). Over the measured range (1-1200 atm), interpretation of the rate data for two of the rings (Phe 45 and Tyr 35) in terms of transition state theory [ 18 ]:

Efficient trajectory simulation methods for diffusional barrier crossing processes

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 multi...