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Molecular Dynamics simulations of a Lennard-Jones system with different range of attraction show that the attractive forces modify the radial distribution of the particles. For condensed liquids only, the forces within the the first coordination shell (FCS) are important, but for gases and moderate condensed fluids, even the attractive forces outside the FCS play a role. The changes in the distribution caused by neglecting the attractive forces, lead to a too high pressure. The weak long-range attractions damp the dynamics and the diffusion of the particles in gas-, super critical fluid- and in liquid states. The values of self-diffusion coefficients (SDC) agree qualitatively with a modified Cohen-Turnbull model. The SDC-s along the critical isotherm show no anomaly at the critical point in agreement with experimental data.

Simulations of objects with classical dynamics are in fact a particular version of discrete dynamics, since almost all the classical dynamics simulations in natural science are performed with the use of the simple "leapfrog" or "Verlet" algorithm. It was, however, Newton who in Principia, Proposition I in 1687 first formulated the discrete algorithm, which much later in 1967 was rederived by L. Verlet. Verlet also formulated a first-order approximation for the velocity v(t) at time t, which has been used in simulations since then. The approximated expressions for v(t) and the kinetic energy lead to severe errors in the thermodynamics at high densities, temperatures, strong repulsive forces, or for large discrete time increments used in discrete "molecular dynamics" (MD) simulations. Here we derive the exact expressions for the discrete dynamics, and show by simulations of a Lennard-Jones system that these expressions now result in equality between temperatures determined from the kinetic energies and the corresponding configurational temperatures determined from the expresssion of Landau and Lifshitz, derived from the forces.

Molecular dynamics simulations of crystallization in a supercooled liquid of Lennard-Jones particles with different range of attractions shows that the inclusion of the attractive forces from the first, second, and third coordination shell increases the trend to crystallize systematic. The bond order Q_{6} in the supercooled liquid is heterogeneously distributed with clusters of particles with relative high bond order for a supercooled liquid, and a systematic increase of the extent of heterogeneity with increasing range of attractions. The onset of crystallization appears in such a cluster, which together explains the attractive forces influence on crystallization. The mean-square displacement and self-diffusion constant exhibit the same dependence on the range of attractions in the dynamics and shows, that the attractive forces and the range of the forces plays an important role for bond ordering, diffusion, and crystallization.

Magnetoelectric (ME) thin film composites consisting of sputtered piezoelectric (PE) and magnetostrictive (MS) layers enable for measurements of magnetic fields passively, i.e. an AC magnetic field directly generates an ME voltage by mechanical coupling of the MS deformation to the PE phase. In order to achieve high field sensitivities a magnetic bias field is necessary to operate at the maximum piezomagnetic coefficient of the MS phase, harnessing mechanical resonances further enhances this direct ME effect size. Despite being able to detect very small AC field amplitudes, exploiting mechanical resonances directly, implies a limitation to available signal bandwidth along with the inherent inability to detect DC or very low frequency magnetic fields. The presented work demonstrates converse ME modulation of thin film Si cantilever composites of mesoscopic dimensions (25 mm × 2.45 mm × 0.35 mm), employing piezoelectric AlN and magnetostrictive FeCoSiB films of 2 µm thickness each. A high frequency mechanical resonance at about 515 kHz leads to strong induced voltages in a surrounding pickup coil with matched self-resonance, leading to field sensitivities up to 64 kV/T. A DC limit of detection of 210 pT/Hz 1/2 as well as about 70 pT/Hz 1/2 at 10 Hz, without the need for a magnetic bias field, pave the way towards biomagnetic applications.

The complex physicochemical structures and chemical reactions in living organism have some common features: (1) The life processes take place in the cytosol in the cells, which, from a physicochemical point of view is an emulsion of biomolecules in a dilute aqueous suspension. (2) All living systems are homochiral with respect to the units of amino acids and carbohydrates, but (some) proteins are chiral unstable in the cytosol. (3) And living organism are mortal. These three common features together give a prerequisite for the prebiotic self-assembly at the start of the Abiogenesis. Here we argue, that it all together indicates, that the prebiotic self-assembly of structures and reactions took place in a more saline environment, whereby the homochirality of proteins not only could be obtained, but also preserved. A more saline environment for the prebiotic self-assembly of organic molecules and establishment of biochemical reactions could have been the hydrothermal vents., (Copyright © 2019. Published by Elsevier Ltd.)

Biosystems contain an almost infinite amount of vital important details, which together ensure their life. There are, however, some common structures and reactions in the systems: the homochirality of carbohydrates and proteins, the metabolism and the genetics. The Abiogenesis, or the origin of life, is probably not a result of a series of single events, but rather the result of a gradual process with increasing complexity of molecules and chemical reactions, and the prebiotic synthesis of molecules might not have left a trace of the establishment of structures and reactions at the beginning of the evolution. But alternatively, one might be able to determine some order in the formation of the chemical denominators in the Abiogenesis. Here we review experimental results and present a model of the start of the Abionenesis, where the spontaneous formation of homochirality in proteins is the precondition for the establishment of homochirality of carbohydrates and for the metabolism at the start of the Abiogenesis., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The peptides in biosystems are polymers of L-amino acids, but they racemize slowly by an active isomerization kinetics. The chemical reactions in biosystems are, however, reversible and here we show by a thermodynamics analysis and by comprehensive Molecular Dynamics simulations of models of peptides, that the isomerization kinetics racemizes the peptides at high water activity, in agreement with experimental observations of aging of peptides, but enhances homochirality at a smaller water activity. The main conclusion of the simulations is that it is only possible to obtain and maintain homochirality in the presence of a hydrophobic compact core in a peptide of hundreds of chiral units and at a low water activity, and thus the establishment of homochirality at the origin of life and aging of proteins in biosystems might be strongly connected., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In 1897 Ostwald formulated his step rule for formation of the most stable crystal state for a system with crystal polymorphism. The rule describes the irreversible way a system converts to the crystal with lowest free energy. But in fact the irreversible way a supercooled gas below the triple point temperature Ttr.p. crystallizes via a liquid droplet is an example of Ostwald's step rule. The homogeneous nucleation in the supersaturated gas is not to a crystal, but to a liquid-like critical nucleus. We have for the first time performed constant energy (NVE) Molecular Dynamics (MD) of homogeneous nucleation without the use of a thermostat. The simulations of homogeneous nucleation in a Lennard-Jones system from supersaturated vapor at temperatures below Ttr.p. reveal that the nucleation to a liquid-like critical nucleus is initiated by a small cold cluster [S. Toxvaerd, J. Chem. Phys. 143, 154705 (2015)]. The release of latent heat at the subsequent droplet growth increases the temperature in the liquid-like droplet, which for not deep supercooling and/or low supersaturation, can exceed Ttr.p.. The temperature of the liquid-like droplet increases less for a low supersaturation and remains below Ttr.p., but without a crystallization of the droplet for long times. The dissipation of the latent heat into the surrounding gas is affected by a traditional MD thermostat, with the consequence that droplet growth is different for (NVE) MD and constant temperature (NVT) MD.

The classical nucleation theory for homogeneous nucleation is formulated as a theory for a density fluctuation in a supersaturated gas at a given temperature. But molecular dynamics simulations reveal that it is small cold clusters which initiates the nucleation. The temperature in the nucleating clusters fluctuates, but the mean temperature remains below the temperature in the supersaturated gas until they reach the critical nucleation size. The critical nuclei have, however, a temperature equal to the supersaturated gas. The kinetics of homogeneous nucleation is not only caused by a grow or shrink by accretion or evaporation of monomers only but also by an exponentially declining change in cluster size per time step equal to the cluster distribution in the supersaturated gas.

For discrete classical Molecular dynamics obtained by the "Verlet" algorithm (VA) with the time increment h there exists a shadow Hamiltonian H̃ with energy Ẽ(h), for which the discrete particle positions lie on the analytic trajectories for H̃. Here, we proof that there, independent of such an analytic analogy, exists an exact hidden energy invariance E(*) for VA dynamics. The fact that the discrete VA dynamics has the same invariances as Newtonian dynamics raises the question, which of the formulations that are correct, or alternatively, the most appropriate formulation of classical dynamics. In this context the relation between the discrete VA dynamics and the (general) discrete dynamics investigated by Lee [Phys. Lett. B 122, 217 (1983)] is presented and discussed.

For discrete classical Molecular Dynamics (MD) obtained by the "Verlet" algorithm (VA) with the time increment h there exists (for sufficiently small h) a shadow Hamiltonian H̃ with energy Ẽ(h), for which the discrete particle positions lie on the analytic trajectories for H̃. The first order estimate of Ẽ(h) is employed to determine the relation with the corresponding energy, E, for the analytic dynamics with h = 0 and the zero-order estimate E0(h) of the energy for discrete dynamics, appearing in the literature for MD with VA. We derive a corresponding time reversible VA algorithm for canonical dynamics for the (NVT̃(h)) ensemble and determine the relations between the energies and temperatures for the different ensembles, including the (NVE0(h)) and (NVT0(h)) ensembles. The differences in the energies and temperatures are proportional with h(2) and they are of the order of a few tenths of a percent for a traditional value of h. The relations between (NVẼ(h)) and (NVE), and (NVT̃(h)) and (NVT) are easily determined for a given density and temperature, and allow for using larger time increments in MD. The accurate determinations of the energies are used to determine the kinetic degrees of freedom in a system of N particles. It is 3N - 3 for a three dimensional system. The knowledge of the degrees of freedom is necessary when simulating small system, e.g., at nucleation.

Pasteur has demonstrated that the chiral components in a racemic mixture can separate in homochiral crystals. But with a strong chiral discrimination the chiral components in a concentrated mixture can also phase separate into homochiral fluid domains, and the isomerization kinetics can then perform a symmetry breaking into one thermodynamical stable homochiral system. Glyceraldehyde has a sufficient chiral discrimination to perform such a symmetry breaking. The requirement of a high concentration of the chiral reactant(s) in an aqueous solution in order to perform and maintain homochirality; the appearance of phosphorylation of almost all carbohydrates in the central machinery of life; the basic ideas that the biochemistry and the glycolysis and gluconeogenesis contain the trace of the biochemical evolution, all point in the direction of that homochirality was obtained just after- or at a phosphorylation of the very first products of the formose reaction, at high concentrations of the reactants in phosphate rich compartments in submarine hydrothermal vents. A racemic solution of D,L-glyceraldehyde-3-phosphate could be the template for obtaining homochiral D-glyceraldehyde-3-phosphate(aq) as well as L-amino acids.

According to standard liquid-state theory repulsive and attractive pair forces play distinct roles for the physics of liquids. This paradigm is put into perspective here by demonstrating a continuous series of pair potentials that have virtually the same structure and dynamics, although only some of them have attractive forces of significance. Our findings reflect the fact that the motion of a given particle is determined by the total force on it, whereas the quantity usually discussed in liquid-state theory is the individual pair force.

The existence of a shadow Hamiltonian H̃ for discrete classical dynamics, obtained by an asymptotic expansion for a discrete symplectic algorithm, is employed to determine the limit of stability for molecular dynamics (MD) simulations with respect to the time-increment h of the discrete dynamics. The investigation is based on the stability of the shadow energy, obtained by including the first term in the asymptotic expansion, and on the exact solution of discrete dynamics for a single harmonic mode. The exact solution of discrete dynamics for a harmonic potential with frequency ω gives a criterion for the limit of stability h ≤ 2/ω. Simulations of the Lennard-Jones system and the viscous Kob-Andersen system show that one can use the limit of stability of the shadow energy or the stability criterion for a harmonic mode on the spectrum of instantaneous frequencies to determine the limit of stability of MD. The method is also used to investigate higher-order central difference algorithms, which are symplectic and also have shadow Hamiltonians, and for which one can also determine the exact criteria for the limit of stability of a single harmonic mode. A fourth-order central difference algorithm gives an improved stability with a factor of 3, but the overhead of computer time is a factor of at least two. The conclusion is that the second-order "Verlet"-algorithm, most commonly used in MD, is superior. It gives the exact dynamics within the limit of the asymptotic expansion and this limit can be estimated either from the conserved shadow energy or from the instantaneous spectrum of harmonic modes.

Classical Newtonian dynamics is analytic and the energy of an isolated system is conserved. The energy of such a system, obtained by the discrete "Verlet" algorithm commonly used in molecular dynamics simulations, fluctuates but is conserved in the mean. This is explained by the existence of a "shadow Hamiltonian" H [S. Toxvaerd, Phys. Rev. E 50, 2271 (1994)], i.e., a Hamiltonian close to the original H with the property that the discrete positions of the Verlet algorithm for H lie on the analytic trajectories of H. The shadow Hamiltonian can be obtained from H by an asymptotic expansion in the time step length. Here we use the first non-trivial term in this expansion to obtain an improved estimate of the discrete values of the energy. The investigation is performed for a representative system with Lennard-Jones pair interactions. The simulations show that inclusion of this term reduces the standard deviation of the energy fluctuations by a factor of 100 for typical values of the time step length. Simulations further show that the energy is conserved for at least one hundred million time steps provided the potential and its first four derivatives are continuous at the cutoff. Finally, we show analytically as well as numerically that energy conservation is not sensitive to round-off errors.

The traditional view that the physical properties of a simple liquid are determined primarily by its repulsive forces was recently challenged by Berthier and Tarjus, who showed that in some cases ignoring the attractions leads to large errors in the dynamics [L. Berthier and G. Tarjus, Phys. Rev. Lett. 103, 170601 (2009); J. Chem. Phys. 134, 214503 (2011)]. We present simulations of the standard Lennard-Jones liquid at several condensed-fluid state points, including a fairly low density state and a very high density state, as well as simulations of the Kob-Andersen binary Lennard-Jones mixture. By varying the range of the forces via a shifted-forces cutoff, results for the thermodynamics, dynamics, and structure show that the determining factor for getting the correct statics and dynamics is not whether or not the attractive forces per se are included in the simulations. What matters is whether or not interactions are included from all particles within the first coordination shell - the attractive forces can thus be ignored, but only at extremely high densities. The recognition of the importance of a local shell in condensed fluids goes back to van der Waals; our results confirm this idea and thereby the basic picture of the old hole and cell theories for simple condensed fluids., (© 2011 American Institute of Physics)

An algorithm is derived for computer simulation of geodesics on the constant-potential-energy hypersurface of a system of N classical particles. First, a basic time-reversible geodesic algorithm is derived by discretizing the geodesic stationarity condition and implementing the constant-potential-energy constraint via standard Lagrangian multipliers. The basic NVU algorithm is tested by single-precision computer simulations of the Lennard-Jones liquid. Excellent numerical stability is obtained if the force cutoff is smoothed and the two initial configurations have identical potential energy within machine precision. Nevertheless, just as for NVE algorithms, stabilizers are needed for very long runs in order to compensate for the accumulation of numerical errors that eventually lead to "entropic drift" of the potential energy towards higher values. A modification of the basic NVU algorithm is introduced that ensures potential-energy and step-length conservation; center-of-mass drift is also eliminated. Analytical arguments confirmed by simulations demonstrate that the modified NVU algorithm is absolutely stable. Finally, we present simulations showing that the NVU algorithm and the standard leap-frog NVE algorithm have identical radial distribution functions for the Lennard-Jones liquid., (© 2011 American Institute of Physics)

In the companion paper [T. S. Ingebrigtsen, S. Toxvaerd, O. J. Heilmann, T. B. Schrøder, and J. C. Dyre, "NVU dynamics. I. Geodesic motion on the constant-potential-energy hypersurface," J. Chem. Phys. (in press)] an algorithm was developed for tracing out a geodesic curve on the constant-potential-energy hypersurface. Here, simulations of NVU dynamics are compared to results for four other dynamics, both deterministic and stochastic. First, NVU dynamics is compared to the standard energy-conserving Newtonian NVE dynamics by simulations of the Kob-Andersen binary Lennard-Jones liquid, its WCA version (i.e., with cut-off's at the pair potential minima), and the Lennard-Jones Gaussian liquid. We find identical results for all quantities probed: radial distribution functions, incoherent intermediate scattering functions, and mean-square displacement as function of time. Arguments are presented for the equivalence of NVU and NVE dynamics in the thermodynamic limit; in particular, to leading order in 1∕N these two dynamics give identical time-autocorrelation functions. In the final part of the paper, NVU dynamics is compared to Monte Carlo dynamics, to a diffusive dynamics of small-step random walks on the constant-potential-energy hypersurface, and to Nosé-Hoover NVT dynamics. If time is scaled for the two stochastic dynamics to make single-particle diffusion constants identical to that of NVE dynamics, the simulations show that all five dynamics are equivalent at low temperatures except at short times., (© 2011 American Institute of Physics)

Simulations involving the Lennard-Jones potential usually employ a cutoff at r = 2.5σ. This communication investigates the possibility of reducing the cutoff. Two different cutoff implementations are compared, the standard shifted potential cutoff and the less commonly used shifted forces cutoff. The first has correct forces below the cutoff, whereas the shifted forces cutoff modifies Newton's equations at all distances. The latter is nevertheless superior; we find that for most purposes realistic simulations may be obtained using a shifted forces cutoff at r = 1.5σ, even though the pair force is here 30 times larger than at r = 2.5σ.

A modification of the constrained equations of motion of Kalibaeva et al. [Mol. Phys. 101, 765 (2003)] in the NPH and NPT ensembles is presented. The modified equations of motion are discretized using central-difference techniques, and the derived integrators are time reversible and conserve the invariant phase space measure. The constraint algorithm builds on the work of Toxvaerd et al. [J. Chem. Phys. 131, 064102 (2009)] in the NVE and NVT ensembles: it thus conserves the holonomic bond constraints at the finite machine precision level in the NPH and NPT ensembles. The algorithms were tested on a system of n=320 ortho-terphenyl molecules, arriving at the target temperature and pressure in a low and high pressure state. Isobaric heat capacities in the NPH and NPT ensembles were calculated for comparison using the fluctuation formulas as well as the thermodynamic definition. The heat capacities agree within the estimated uncertainties.

Results from molecular dynamics simulations of two viscous molecular model liquids--the Lewis-Wahnström model of orthoterphenyl and an asymmetric dumbbell model--are reported. We demonstrate that the liquids have a "hidden" approximate scale invariance: equilibrium potential energy fluctuations are accurately described by inverse power-law (IPL) potentials, the radial distribution functions are accurately reproduced by the IPL's, and the radial distribution functions obey the IPL predicted scaling properties to a good approximation. IPL scaling of the dynamics also applies--with the scaling exponent predicted by the equilibrium fluctuations. In contrast, the equation of state does not obey the IPL scaling. We argue that our results are general for van der Waals liquids, but do not apply, e.g., for hydrogen-bonded liquids.

Time-reversible molecular dynamics algorithms with bond constraints are derived. The algorithms are stable with and without a thermostat and in double precision as well as in single-precision arithmetic. Time reversibility is achieved by applying a central-difference expression for the velocities in the expression for Gauss' principle of least constraint. The imposed time symmetry results in a quadratic expression for the Lagrange multiplier. For a system of complex molecules with connected constraints the corresponding set of coupled quadratic equations is easily solved by a consecutive iteration scheme. The algorithms were tested on two models. One is a dumbbell model of Toluene, the other system consists of molecules with four connected constraints forming a triangle and a branch point of constraints. The equilibrium particle distributions and the mean-square particle displacements for the dumbbell model were compared to the corresponding functions obtained by GROMACS. The agreement is perfect within statistical error.

Recently, the supercooled Wahnstrom binary Lennard-Jones mixture was partially crystallized into MgZn(2) phase crystals in lengthy molecular dynamics simulations. We present molecular dynamics simulations of a modified Kob-Andersen binary Lennard-Jones mixture that also crystallizes in lengthy simulations here, however, by forming pure fcc crystals of the majority component. The two findings motivate this paper that gives a general thermodynamic and kinetic treatment of the stability of supercooled binary mixtures, emphasizing the importance of negative mixing enthalpy whenever present. The theory is used to estimate the crystallization time in a Kob-Andersen mixture from the crystallization time in a series of related systems. At T=0.40 we estimate this time to be 5x10(7) time units ( approximately 0.1 ms). A new binary Lennard-Jones mixture is proposed that is not prone to crystallization and faster to simulate than the two standard binary Lennard-Jones mixtures. This is obtained by removing the like-particle attractions by switching to Weeks-Chandler-Andersen type potentials, while maintaining the unlike-particle attraction.

Experimental data for a series of central and simple molecules in biosystems show that some amino acids and a simple sugar molecule have a chiral discrimination in favor of homochirality. Models for segregation of racemic mixtures of chiral amphiphiles and lipophiles in aqueous solutions show that the amphiphiles with an active isomerization kinetics can perform a spontaneous break of symmetry during the segregation and self-assembly to homochiral matter. Based on this observation it is argued that biomolecules with a sufficiently strong chiral discrimination could be the origin of homochirality in biological systems.

The article explores the possibility that the ordering of bio-organic molecules into a homochiral assembly at the origin of life was performed not in aqueous solutions of amino acids or related materials but in racemic glyceraldehyde in the "formose" reaction at high concentration and temperature. Based on physical chemical evidence and computer simulations of condensed fluids, it is argued that the isomerization kinetics of glyceraldehyde is responszible of the symmetry break and the ordering of molecules into homochiral domains.

The model for domain catalyzed isomerization kinetics in condensed fluids is applied for a diluted mixture of a chiral solute with a consolute temperature. The solution is quench to phase separation at temperatures below the consolute temperature. The droplet coalescence enhances the isomerization kinetics due to the substantial excess pressure inside the small droplets given by the Laplace equation. The domain catalyzed isomerization kinetics breaks the symmetry, and the droplets end with only one dominating species. We argue that D-glyceraldehyde which is only moderately solvable in water and which has played a crucial role in the evolution is a candidate for the stereo specific ordering in bio-organic matter.

Simulations of different reaction schemes for isomerization kinetics in a condensed fluid mixture between two species with small differences in the pair energies show that one of the species dominates at late reaction times. The isomerization is performed on the basis of the energy of the two states, either by choosing minimum energy or by use of Boltzmann weighted kinetics. Both kinetics are autocatalytic and establish domain decomposition with critical fluctuations, which ensure the symmetry break. The model(s) offers a possible explanation of the origin of biomolecular chirality.

The dynamics of Rhizomucor miehei lipase has been studied by molecular dynamics simulations at temperatures ranging from 200-500K. Simulations carried out in periodic boundary conditions and using explicit water molecules were performed for 400 ps at each temperature. Our results indicate that conformational changes and internal motions in the protein are significantly influenced by the temperature increase. With increasing temperature, the number of internal hydrogen bonds decreases, while surface accessibility, radius of gyration and the number of residues in random coil conformation increase. In the temperature range studied, the motions can be described in a low dimensional subspace, whose dimensionality decreases with increasing temperature. Approximately 80% of the total motion is described by the first (i) 80 eigenvectors at T=200K, (ii) 30 eigenvectors at T=300K and (iii) 10 eigenvectors at T=400K. At high temperature, the alpha-helix covering the active site in the native Rhizomucor miehei lipase, the helix at which end the active site is located, and in particular, the loop (Gly35-Lys50) show extensive flexibility.

We have investigated the binding properties of and dynamics in Humicola lanuginosa lipase (Hll) and the inactive mutant S146A (active Ser146 substituted with Ala) using fluorescence spectroscopy and molecular dynamics simulations, respectively. Hll and S146A show significantly different binding behavior for phosphatidylcholine (PC) and phosphatidylglycerol (PG) liposomes. Generally, higher binding affinity is observed for Hll than the S146A mutant. Furthermore, depending on the matrix, the addition of the transition state analogue benzene boronic acid increases the binding affinity of S146A, whereas only small changes are observed for Hll suggesting that the active site lid in the latter opens more easily and hence more lipase molecules are bound to the liposomes. These observations are in agreement with molecular dynamics simulations and subsequent essential dynamics analyses. The results reveal that the hinges of the active site lid are more flexible in the wild-type Hll than in S146A. In contrast, larger fluctuations are observed in the middle region of the active site loop in S146A than in Hll. These findings reveal that the single mutation (S146A) of the active site serine leads to substantial conformational alterations in the H. lanuginosa lipase and different binding affinities.

We have investigated the activation pathway of three wild type lipases and three mutants using molecular dynamics techniques combined with a constrained mechanical protocol. The activation of these lipases involves a rigid body hinge-type motion of a single helix, which is displaced during activation to expose the active site and give access to the substrate. Our results suggest that the activation of lipases is enhanced in a hydrophobic environment as is generally observed in experiments. The energy gain upon activation varies between the different lipases and depends strongly on the distribution of the charged residues in the activating loop region. In a low dielectric constant medium (such as a lipid environment), the electrostatic interactions between the residues located in the vicinity of the activating loop (lipid contact zone) are dominant and determine the activation of the lipases. Calculations of the pKas qualitatively indicate that some titratable residues experience significant pK shifts upon activation. These calculations may provide sufficient details for an understanding of the origin and magnitude of a given electrostatic effect and may provide an avenue for exploring the activation pathway of lipases.

We have investigated the effect of different solvents on the dynamics of Rhizomucor miehei lipase. Molecular dynamics simulations were performed in water, methyl hexanoate, and cyclohexane. Analysis of the 400-ps trajectories showed that the solvent has a pronounced effect on the geometrical properties of the protein. The radius of gyration and total accessibility surface decrease in organic solvents, whereas the number of hydrogen bonds increases. The essential motions of the protein in different solvents can be described in a low-dimensional "essential subspace," and the dynamic behavior in this subspace correlates with the polarity of the solvent. Methyl hexanoate, which is a substrate for R. miehei lipase, significantly increases the fluctuations in the active-site loop. During the simulation, a methyl hexanoate entered the active-site groove. This observation provides insight into the possible docking mechanism of the substrate.

We have investigated the role of the substrate on the interfacial activation of lipases by an interdisciplinary study of the structure and dynamics of 1,2-sn dipalmitoylglycerol monolayers at distinct surface pressures. The diglyceride Langmuir film undergoes two phase transitions occurring at 38.3 and 39.8 A2 per molecule. The first transition is unique for diglyceride molecules and is driven by a reorganization of the headgroups causing a change in the hydrophobicity of the oil-water interface. X-ray diffraction studies of different mesophases shows that in the two highest pressure phases, the alkyl chains pack in an hexagonal structure relaxing to a distorted-hexagonal lattice in the lowest pressure phase with the alkyl chains tilted by approximately 14 degrees in a direction close to a nearest neighbour direction.