Accelerating molecular simulations by reversible mapping between local minima

A new framework is presented for performing Monte Carlo simulations of condensed matter based on a recently developed bijective mapping between local energy minima. The framework is used to implement a range of new multiparticle Monte Carlo moves, which are investigated by simulating atomic Lennard-Jones fluids in the canonical and grand canonical ensembles. Important aspects of the simulation protocol and their effect on performance are analyzed in detail. Using the mapping accelerates the simulations by many orders of magnitude when compared to the equivalent moves without the mapping, and leads to particularly efficient configurational sampling at low temperatures and high densities. The method appears to be suitable for adapting to quantitative simulations of more complex molecular systems over long effective time scales.     

Potential-hypersurface local minima and temperature

Summary The presence of several local energy minima on a potential hypersurface is treated in terms of geometry, energy, and harmonic vibrations. Partition functions of the minima are employed in order to treat temperature excitations of rotational-vibrational motions. Proportions of relative stabilities of the individual structures change with temperature (including interchanges of the relative stabilities so that the global energy minimum can even be less populated than a higher local energy minimum). Illustrative examples are given on B₂H₄ and Ga₂H₄ systems. The treatment is suggested as a standard complement of the local-minimum hypersurface representation (before whole potential hypersurfaces are constructed and employed in molecular dynamics treatments).Dedicated to Prof. Klaus Ruedenberg on the occasion of his 70th birthday     

Particle rearrangements during transitions between local minima of the potential energy landscape of a binary Lennard-Jones liquid

The potential energy landscape (PEL) of binary Lennard-Jones (BLJ) mixtures exhibits local minima, or inherent structures (IS), which are organized into metabasins (MBs). We study the particle rearrangements related to transitions between both successive IS and successive MB for a small 80:20 BLJ system near the mode-coupling temperature TMCT. The analysis includes the displacements of individual particles, the localization of the rearrangements, and the relevance of string-like motion. We find that the particle rearrangements during IS and MB transitions do not change significantly at TMCT. In particular, an onset of single particle hopping on the length scale of the interparticle distance is not observed. Further, it is demonstrated that IS and MB dynamics are spatially heterogeneous and facilitated by string-like motion. To investigate the mechanism of string-like motion, we follow the particle rearrangements during suitable sequences of IS transitions. We find that most strings observed after a series of transitions do not move coherently during a single transition, but subunits of different sizes are active at different times. Several findings suggest that, though string-like motion is of comparable relevance when the system explores a MB and when it moves from one MB to another, the occurrence of a successful string enables the system to exit a MB. Moreover, we show that the particle rearrangements during two consecutive MB transitions are basically uncorrelated. In particular, different groups of particles are highly mobile. We further find the positions of strings during successive MB transitions weakly but positively correlated, supporting the idea of dynamic facilitation. Finally, the relation between the features of the potential energy landscape and the relaxation processes in supercooled liquids is discussed.     

Finding transition pathways using the string method with swarms of trajectories

An approach to find transition pathways in complex systems is presented. The method, which is related to the string method in collective variables of Maragliano et al. (J. Chem. Phys. 2006, 125, 024106), is conceptually simple and straightforward to implement. It consists of refining a putative transition path in the multidimensional space supported by a set of collective variables using the average dynamic drift of those variables. This drift is estimated on-the-fly via swarms of short unbiased trajectories started at different points along the path. Successive iterations of this algorithm, which can be naturally distributed over many computer nodes with negligible interprocessor communication, refine an initial trial path toward the most probable transition path (MPTP) between two stable basins. The method is first tested by determining the pathway for the C7eq to C7ax transition in an all-atom model of the alanine dipeptide in vacuum, which has been studied previously with the string method in collective variables. A transition path is found with a committor distribution peaked at 1/2 near the free energy maximum, in accord with previous results. Last, the method is applied to the allosteric conformational change in the nitrogen regulatory protein C (NtrC), represented here with a two-state elastic network model. Even though more than 550 collective variables are used to describe the conformational change, the path converges rapidly. Again, the committor distribution is found to be peaked around 1/2 near the free energy maximum between the two stable states, confirming that a genuine transition state has been localized in this complex multidimensional system.     

Molecular mechanics study of myelin basic protein peptide 87-118: Some local energy minima

Myelin basic protein (MBP) is the major extrinsic protein of the myelin sheath in the central nervous system. It is this protein that is destroyed in such demyelinating diseases as multiple sclerosis. We have examined the predicted structures of one segment of MBP using the molecular mechanics program ECEPP83 developed by Scheraga and co-workers as modified by Chuman, Momany, and Schafer. We have focused upon a segment, 87-118, containing the Pro-Pro-Pro sequence (residues 100–102), which has been predicted from standard algorithms to exist in a hairpin loop connecting anti-parallel beta-strands. Several local energy minima have been found and reported. Tripoline sequences are not rare in proteins, but their structure and function is still uncertain.     

An empirically adjusted Newton–Raphson algorithm for finding local minima on molecular potential energy surfaces

A simple extension of the Newton–Raphson method is proposed that approximately accounts for anharmonicity in bond-stretching coordinates. By modeling each bonded distance in a polyatomic molecule as a Morse oscillator with no anharmonic stretch-stretch or stretch-bend coupling, a multiplicative correction factor to the Newton–Raphson step is derived. Representative examples suggest that the rate of convergence of the proposed scheme is typically faster than that of the standard Newton–Raphson method.     

Finding the global minima of (Ne)n clusters with non-empirical models: a comparison of results

The energetics and the structural properties of some of the smaller ionic clusters of neon atoms (Ne_n⁺, with n up to 25) are examined using different modeling for the interactions within each cluster moiety. A new, very simple model for the global interaction, the polygon growth model or PGM, is presented and discussed in detail. The results of the calculations, and the physical reliability of the methods, are then examined in comparison with earlier theoretical results and with some available experimental data. In spite of the simplicity of the PGM scheme, the present treatment shows it to be able to reproduce all the important features known for these clusters from earlier calculations and from measurements.     

Cytotoxic Withaphysalins from Physalis minima

A novel withanolide, withaphysalin P ( 1 ) with a nine‐membered ring, and six other new withaphysalins, 2 – 7 , together with the three known withaphysalins 8 – 10 were isolated from Physalis minima L. The structures were deduced by means of spectroscopic analyses, and that of withaphysalin P ( 1 ) was confirmed by a single‐crystal X‐ray diffraction analysis. Plausible biosynthetic pathways were postulated (Scheme 1). All compounds were tested for their antiproliferative activities toward the human colorectal‐carcinoma HCT‐116 cells and human nonsmall‐cell lung‐cancer NCI‐H460 cells (Table 4). Compounds 1 – 3, 7 – 10, 7a , and 7b displayed moderate cytotoxic activity against the two human cancer cell lines.     

Calculating all local minima on liquidus surfaces using the FactSage software and databases and the Mesh Adaptive Direct Search algorithm

It is often of interest, for a multicomponent system, to identify the low melting compositions at which local minima of the liquidus surface occur. The experimental determination of these minima can be very time-consuming. An alternative is to employ the CALPHAD approach using evaluated thermodynamic databases containing optimized model parameters giving the thermodynamic properties of all phases as functions of composition and temperature. Liquidus temperatures are then calculated by Gibbs free energy minimization algorithms which access the databases. Several such large databases for many multicomponent systems have been developed over the last 40 years, and calculated liquidus temperatures are generally quite accurate. In principle, one could then search for local liquidus minima by simply calculating liquidus temperatures over a compositional grid. In practice, such an approach is prohibitively time-consuming for all but the simplest systems since the required number of grid points is extremely large. In the present article, the FactSage database computing system is coupled with the powerful Mesh Adaptive Direct Search (MADS) algorithm in order to search for and calculate automatically all liquidus minima in a multicomponent system. Sample calculations for a 4-component oxide system, a 7-component chloride system, and a 9-component ferrous alloy system are presented. It is shown that the algorithm is robust and rapid.     

Locating seam minima for macromolecular systems

The performance of three different functions (penalty, Lagrange–Newton, and projection) used in combination with three different Newton-based optimization algorithms for solving large-scale constrained optimizations is investigated. The test cases correspond to locating minima on seams between two force field energy functions, which can be used to model transitions structures in chemical reactions. The Lagrange–Newton function used in combination with a standard Newton–Raphson optimization is found to be the most efficient for systems up to ～500 atoms, while an iterative algorithm becomes preferable for larger systems.     

New Thymol Derivate from Centipeda minima

1 Introduction Centipeda minima(Compositae) is an annual herbaceous plant found in moist places throughout the plains mainly in the southern regions of the People’s Republic of China, Eastern tropical Asia, Australia     

New leishmanicidal physalins from Physalis minima

Two new physalins, 16,24-cyclo-13,14-secoergosta-2-ene-18,26-dioic acid-14 : 17,14 : 27-diepoxy-11beta,13,20,22-tetrahydroxy-5alpha-methoxy-1,15-dioxo-gamma-lactone delta-lactone (1), and 16,24-cyclo-13,14-secoergosta-2-ene-18,26-dioic acid-14 : 17,14 : 27-diepoxy-5alpha,11beta,13,20,22-pentahydroxy-1,6,15-trioxo-gamma-lactone delta-lactone (2), have been isolated from the whole plant of Physalis minima Linn. (var. indica). Their structures were deduced on the basis of spectroscopic analysis. Both of these compounds have shown potent leishmanicidal activity against the promastigotes of Leishmania major.     

Antibacterial thymol derivatives isolated from Centipeda minima

Two new monoterpenoids, 8,10-dihydroxy-9(2)-methylbutyryloxythymol (1) and 10-hydroxy-8,9-dioxyisopropylidene-thymol (2), together with five known thymol derivatives: 8,9,10-trihydroxythymol (3), thymol-beta-glucopyranoside (4), 9-hydroxythymol (5), 8,10-dihydroxy-9-isobutyryloxythymol (6), and 8-hydroxy-9,10-diisobutyryloxythymol (7), were isolated from Centipeda minima. Their structures were identified by means of spectroscopic analyses. Interestingly, compound 2 is not an extraction artifact according to a close HPLC examination of material after extraction by analytical MeOH at ambient temperature. The antibacterial activities of compounds 1-7 were evaluated against eight microbial strains by the agar dilution method.     

New insights into the multiple minima problem

Minima distribution of thorough conformational searches of three peptides of different length ranging from five to nine residues, were compared with the density of states of a flexible molecule derived from the rotational isomeric approximation. It is observed that minima distributions generated from the conformational searches exhibit the same characteristics as the density of states derived from the rotational isomeric model: an asymmetric distribution with a maximum. These results together with a more profound understanding of the characteristics of the energy landscapes of polypeptides, provide new insights into the multiple minima problem. The implications in devising more robust conformational search strategies are discussed.     

Distinguishing between pathways for transmetalation in Suzuki-Miyaura reactions

We report a systematic study of the stoichiometric reactions of isolated arylpalladium hydroxo and halide complexes with arylboronic acids and aryltrihydroxyborates to evaluate the relative rates of the two reaction pathways commonly proposed to account for transmetalation in the Suzuki-Miyaura reaction. On the basis of the relative populations of the palladium and organoboron species generated under conditions common for the catalytic process and the observed rate constants for the stoichiometric reactions between the two classes of reaction components, we conclude that the reaction of a palladium hydroxo complex with boronic acid, not the reaction of a palladium halide complex with trihydroxyborate, accounts for transmetalation in catalytic Suzuki-Miyaura reactions conducted with weak base and aqueous solvent mixtures.     

A systematic study of minima in alanine dipeptide

The alanine dipeptide is a standard system to model dihedral angles in proteins. It is shown that obtaining the Ramachandran plot accurately is a hard problem because of many local minima; depending on the details of geometry optimizations, different Ramachandran plots can be obtained. To locate all energy minima, starting from geometries from MD simulations, 250,000 geometry optimizations were performed at the level of RHF/6-31G*, followed by re-optimizations of the located 827 minima at the level of MP2/6–311++G**, yielding 30 unique minima, most of which were not previously reported in literature. Both in vacuo and solvated structures are discussed. The minima are systematically categorized based on four backbone dihedral angles. The Gibbs energies are evaluated and the structural factors determining the relative stabilities of conformers are discussed. © 2018 Wiley Periodicals, Inc.