Recent advances in protein conformation sampling by combining machine learning with molecular simulation

The rapid advancement and broad application of machine learning(ML)have driven a groundbreaking revolution in computational biology.One of the most cutting-edge and important applications of ML is its integration with molecular simulations to improve the sampling efficiency of the vast conformational space of large biomolecules.This review focuses on recent studies that utilize ML-based techniques in the exploration of protein conformational landscape.We first highlight the recent development of ML-aided enhanced sampling methods,including heuristic algorithms and neural networks that are designed to refine the selection of reaction coordinates for the construction of bias potential,or facilitate the exploration of the unsampled region of the energy landscape.Further,we review the development of autoencoder based methods that combine molecular simulations and deep learning to expand the search for protein conformations.Lastly,we discuss the cutting-edge methodologies for the one-shot generation of protein conformations with precise Boltzmann weights.Collectively,this review demonstrates the promising potential of machine learning in revolutionizing our insight into the complex conformational ensembles of proteins.

First-Principles Studies of Structural Evolutions in Cathode Materials LiMO_(2)(M=Co,Mn,Ni)

We explore the structural evolutions of stoichiometric LiMO_(2)using the first-principles calculations combined with the cluster expansion method.We automatically obtain the ground state structures of the stoichiometric LiMO_(2)by just considering the cation orderings in the quasi rock-salt structures and the following structural relaxations due to both the atomic size mismatches and the Jahn–Teller distortions.We point out that,on the one hand,the cation orderings are mainly determined by the nearest,the second nearest,and the third nearest cation interactions and can be obtained from the‘phase diagram’we have built using the relative strengths of effective cluster interaction(ECI).On the other hand,the structural relaxations are dominated by the crystal field splitting(CFS)energies,i.e.,structures with larger CFS energies are more stable.By calculating the ECIs and CFS energies for various structures of LiMO_(2),we clearly show how ECI and CFS play roles in determining the structural evolution mechanism of these systems.

Orbital-Ordering Driven Simultaneous Tunability of Magnetism and Electric Polarization in Strained Monolayer VCl_(3)

Two-dimensional(2D)van der Waals magnetic materials have promising and versatile electronic and magnetic properties in the 2D limit,indicating a considerable potential to advance spintronic applications.Theoretical predictions thus far have not ascertained whether monolayer VCl_(3) is a ferromagnetic(FM)or anti-FM monolayer;this also remains to be experimentally verified.We theoretically investigate the influence of potential factors,including C_(3) symmetry breaking,orbital ordering,epitaxial strain,and charge doping,on the magnetic ground state.Utilizing first-principles calculations,we predict a collinear type-Ⅲ FM ground state in monolayer VCl_(3) with a broken C_(3) symmetry,wherein only the former two of three t_(2g)orbitals(a_(1g),e_(g2)^(π)and e_(g1)^(π))are occupied.The atomic layer thickness and bond angles of monolayer VCl_(3) undergo abrupt changes driven by an orbital ordering switch,resulting in concomitant structural and magnetic phase transitions.Introducing doping to the underlying Cl atoms of monolayer VCl_(3) without C_(3) symmetry simultaneously induces in-and out-of-plane polarizations.This can achieve a multiferroic phase transition if combined with the discovered adjustments of magnetic ground state and polarization magnitude under strain.The establishment of an orbital-ordering driven regulatory mechanism can facilitate deeper exploration and comprehension of magnetic properties of strongly correlated systems in monolayer VCl_(3).

Intrinsic Instability of the Hybrid Halide Perovskite Semiconductor CH3NH3PbI3

The organic-inorganic hybrid perovskite CH3NH3PbI3 has attracted significant interest for its high performance in converting solar light into electrical power with an efficiency exceeding 20%. Unfortunately, chemical stability is one major challenge in the development of CH3NH3PbI3 solar cells. It was commonly assumed that moisture or oxygen in the environment causes the poor stability of hybrid halide perovskites, however, here we show from the first-principles calculations that the room-temperature tetragonal phase of CH3NH3PbI3 is thermodynamically unstable with respect to the phase separation into CH3NH3I ＋ PbI2, i.e., the disproportionation is exothermic, independent of the humidity or oxygen in the atmosphere. When the structure is distorted to the low-temperature orthorhombie phase, the energetic cost of separation increases, but remains small. Contributions from vibrational and configurational entropy at room temperature have been considered, but the instability of CH3NH3PbI3 is unchanged. When I is replaced by Br or CI, Pb by Sn, or the organic cation CH3NH3 by inorganic Cs, the perovskites become more stable and do not phase-separate spontaneously. Our study highlights that the poor chemical stability is intrinsic to CH3NH3PbI3 and suggests that element-substitution may solve the chemical stability problem in hybrid halide perovskite solar cells.

Amyloid-β peptide aggregation and the influence of carbon nanoparticles

Soluble peptides or proteins can self-aggregate into insoluble, ordered amyloid fibrils under appropriate conditions. These amyloid aggregates are the hallmarks of several human diseases ranging from neurodegenerative disorders to sys- temic amyloidoses. In this review, we first introduce the common structural features of amyloid fibrils and the amyloid fibrillation kinetics determined from experimental studies. Then, we discuss the structural models of Alzheimer＇s amyloid- β （Aβ） fibrils derived from solid-state nuclear magnetic resonance spectroscopy. On the computational side, molecular dynamics simulations can provide atomic details of structures and the underlying oligomerization mechanisms. We finally summarize recent progress in atomistic simulation studies on the oligomerization of β （including full-length Af and its fragments） and the influence of carbon nanoparticles.

The mechanism of hydrogen abstraction by high valence transition metal oxo compounds

We present here a systematic theoretical study to explore the underlying mechanisms of the H abstraction reaction from methane. Various abstracting agents have been modeled, using oxygen radicals and a set of high valence metal oxo compounds. Our calculations demonstrate that although H abstraction from CH3-H by metal oxoes can be satisfactorily fitted into the Polanyi correlation on the basis of oxygen radicals, the mechanisms behind are significantly different. The frontier orbital analyses show that there are three electrons and three active orbitals (3e, 3o) involved in H abstraction by oxygen radicals; whereas an additional orbital of pi(M-O)* is involved in H abstraction by M = O, resulting in a (4e, 4o) interaction. In terms of valence bond state correlation diagram, we find that H abstraction by a metal oxo may benefit from the contribution of ionic resonance structures, which could compensate the penalty of opening the M-O pbond. We believe that these findings can help to design more effective catalysts for the activation of light alkanes. (C) 2016 Science Press and Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Published by Elsevier B. V. and Science Press. All rights reserved.

Unexpected low thermal conductivity and large power factor in Dirac semimetal Cd3As2

Thermoelectrics has long been considered as a promising way of power generation for the next decades. So far, extensive efforts have been devoted to the search of ideal thermoelectric materials, which require both high electrical conductivity and low thermal conductivity. Recently, the emerging Dirac semimetal Cd3As2, a three-dimensional analogue of graphene, has been reported to host ultra-high mobility and good electrical conductivity as metals. Here, we report the observation of unexpected low thermal conductivity in Cd3As2, one order of magnitude lower than the conventional metals or semimetals with a similar electrical conductivity, despite the semimetal band structure and high electron mobility. The power factor also reaches a large value of 1.58 mW.m 1 .K-2 at room temperature and remains non-saturated up to 400 K. Corroborating with the first-principles calculations, we find that the thermoelectric performance can be well-modulated by the carrier concentration in a wide range. This work demonstrates the Dirac semimetal Cd3As2 as a potential candidate of thermoelectric materials.

Theoretical Studies on Dehydrogenation Reactions in Mg2（BH4）2（NH2）2 Compounds

Borohydrides have been recently hightlighted as prospective new materials due to their high gravimetric capacities for hydrogen storage. It is, therefore, important to under- stand the underlying dehydrogenation mechanisms for further development of these ma- terials. We present a systematic theoretical investigation on the dehydrogenation mecha- nisms of the Mg2（BH4）2（NH2）2 compounds. We found that dehydrogenation takes place most likely via the intermolecular process, which is favorable both kinetically and thermo- dynamically in comparison with that of the intramolecular process. The dehydrogenation of Mg2（BH4）2（NH2）2 initially takes place via the direct combination of the hydridie H in BH4 and the protie H in NH2-, followed by the formation of Mg-H and subsequent ionic recombination of Mg-Hδ-…Hδ＋-N.

Intrinsic Features of an Ideal Glass

In order to understand the long-standing problem of the nature of glass states, we perform intensive simulations on the thermodynamic properties and potential energy surface of an ideal glass. It is found that the atoms of an ideal glass manifest cooperative diffusion, and show clearly different behavior from the liquid state. By determining the potential energy surface, we demonstrate that the glass state has a fiat potential landscape, which is the critical intrinsic feature of ideal glasses. When this potential region is accessible through any thermal or kinetic process, the glass state can be formed and a glass transition will occur, regardless of any special structural character. With this picture, the glass transition can be interpreted by the emergence of conlgurational entropies, as a consequence of flat potential landscapes.

Bending energy of a vesicle to which a small spherical particle adhere:An analytical study

On the basis of Helfrich＇s bending energy model, we show that the adsorption process of a small spherical particle to a closed vesicle can be analytically studied by retaining the leading terms in an expansion of the shape equation. Our general derivation predicts the optimal binding sites on a vesicle, where the local membrane shape of the binding site could be non-axisymmetric before the continuous adhesion transition takes place. Our derivation avoids directly solving the shape equation and depends on an integration of the contact-line condition. The results are verified by several examples of independent numerical solutions.

Contrasting Magnetism in Isovalent Layered LaSr3NiRuO4H4 and LaSrNiRuO4 due to Distinct Spin-Orbital States

The recently synthesized first 4d transition-metal oxide-hydride LaSr3NiRuO4H4 with the unusual high H:O ratio surprisingly displays no magnetic order down to 1.8 K. This is in sharp contrast to the similar unusual low-valent Ni^+-Ru^2+ layered oxide LaSrNiRuO4 which has a rather high ferromagnetic(FM) ordering Curie temperature TC^250 K. Using density functional calculations with the aid of crystal field level diagrams and superexchange pictures, we find that the contrasting magnetism is due to the distinct spin-orbital states of the Ru^2+ions(in addition to the common Ni+S = 1/2 state but with a different orbital state): the Ru^2+S = 0 state in LaSr3NiRuO4H4, but the Ru^2+S= 1 state in LaSrNiRuO4. The Ru^2+S = 0 state has the(xy)^2(xz, yz)^4 occupation due to the RuH4O2 octahedral coordination, and then the nonmagnetic Ru2+ions dilute the S= 1/2 Ni^+ sublattice which consequently has a very weak antiferromagnetic superexchange and thus accounts for the presence of no magnetic order down to 1.8 K in LaSr3NiRuO4H4. In strong contrast, the Ru^2+S = 1 state in LaSrNiRuO4 has the(3z^2-r^2)^2(xz, yz)^3(xy)^1 occupation due to the planar square RuO4 coordination, and then the multi-orbital FM superexchange between the S= 1/2 Ni^+ and S= 1 Ru^2+ions gives rise to the high TC in LaSrNiRuO4. This work highlights the importance of spin-orbital states in determining the distinct magnetism.

Structural and dynamical mechanisms of a naturally occurring variant of the human prion protein in preventing prion conversion

Prion diseases are associated with the misfolding of the normal helical cellular form of prion protein (PrPC) into the β-sheet-rich scrapie form (PrPSc) and the subsequent aggregation of PrPSc into amyloid fibrils. Recent studies demonstrated that a naturally occurring variant V127 of human PrPC is intrinsically resistant to prion conversion and aggregation, and can completely prevent prion diseases. However, the underlying molecular mechanism remains elusive. Herein we perform multiple microsecond molecular dynamics simulations on both wildtype (WT) and V127 variant of human PrPC to understand at atomic level the protective effect of V127 variant. Our simulations show that G127V mutation not only increases the rigidity of the S2–H2 loop between strand-2 (S2) and helix-2 (H2), but also allosterically enhances the stability of the H2 C-terminal region. Interestingly, previous studies reported that animals with rigid S2–H2 loop usually do not develop prion diseases, and the increase in H2 C-terminal stability can prevent misfolding and oligomerization of prion protein. The allosteric paths from G/V127 to H2 C-terminal region are identified using dynamical network analyses. Moreover, community network analyses illustrate that G127V mutation enhances the global correlations and intra-molecular interactions of PrP, thus stabilizing the overall PrPC structure and inhibiting its conversion into PrPSc. This study provides mechanistic understanding of human V127 variant in preventing prion conversion which may be helpful for the rational design of potent anti-prion compounds.

The XPK Package:A Comparison between the Extended Phenomenological Kinetic(XPK) Method and the Conventional Kinetic Monte Carlo(KMC) Method

Recently, we proposed the extended phenomenological kinetics (XPK) method, which overcomes the notorious timescale separation difficulty between fast diffusion and slow chemical reactions in conventional kinetic Monte Carlo (KMC) simulations. In the present work, we make a comprehensive comparison, based on the newly developed XPK package, between the XPK method and the conventional KMC method using a model hydrogenation reaction system. Two potential energy surfaces with different lateral interactions have been designed to illustrate the advantages of the XPK method in computational costs, parallel efficiency and the convergence behaviors to steady states. The XPK method is shown to be efficient and accurate, holding the great promise for theoretical modelling in heterogeneous catalysis, in particular, when the role of the lateral interactions among adsorbates is crucial.

Superexchange Interactions and Magnetic Anisotropy in MnPSe_(3)Monolayer

Two-dimensional van der Waals magnetic materials are of great current interest for their promising applications in spintronics.Using density functional theory calculations in combination with the maximally localized Wannier functions method and the magnetic anisotropy analyses,we study the electronic and magnetic properties of MnPSe_(3)monolayer.Our results show that it is a charge transfer antiferromagnetic(AF)insulator.For this Mn^(2)+3d^(5)system,although it seems straightforward to explain the AF ground state using the direct exchange,we find that the nearly 90oMn-Se-Mn charge transfer type superexchange plays a dominant role in stabilizing the AF ground state.Moreover,our results indicate that,although the shape anisotropy favors an out-of-plane spin orientation,the spin-orbit coupling(SOC)leads to the experimentally observed in-plane spin orientation.We prove that the actual dominant contribution to the magnetic anisotropy comes from the second-order perturbation of the SOC,by analyzing its distribution over the reciprocal space.Using the AF exchange and anisotropy parameters obtained from our calculations,our Monte Carlo simulations give the Néel temperature T_(N)=47 K for MnPSe_(3)monolayer,which agrees with the experimental 40 K.Furthermore,our calculations show that under a uniaxial tensile(compressive)strain,Néel vector would be parallel(perpendicular)to the strain direction,which well reproduces the recent experiments.We also predict that T_(N)would be increased by a compressive strain.

Interplay of Strain and Magnetism in FeSe Monolayers

Superconductivity and its relationship with strain remains elusive in the monolayer FeSe superconductor. Based on first-principles calculations and model studies, we investigate the magnetic properties of FeSe and FeTe monolayers and find that tensile strain induces changes to magnetic phases for both materials. Furthermore, we reveal that electron doping will decrease the difference of effective magnetic interactions between the a and b directions in an FeSe monolayer and hence suppress its nematicity. We suggest that the overall effect of tensile strain combined with electron doping hinders the appearance of both magnetic and nematic orders in an FeSe monolayer,which paves the way for the emergence of superconductivity.

Directly Determining the Interface Structure and Band Offset of a Large-Lattice-Mismatched CdS/CdTe Heterostructure

The CdS/CdTe heterojunction plays an important role in determining the energy conversion efficiency of CdTe solar cells.However,the interface structure remains unknown,due to the large lattice mismatch between CdS and CdTe,posing great challenges to achieving an understanding of its interfacial effects.By combining a neuralnetwork-based machine-learning method and the stochastic surface walking-based global optimization method,we first train a neural network potential for CdSTe systems with demonstrated robustness and reliability.Based on the above potential,we then use simulated annealing to obtain the optimal structure of the CdS/CdTe interface.We find that the most stable structure has the features of both bulks and disorders.Using the obtained structure,we directly calculate the band offset between CdS and CdTe by aligning the core levels in the heterostructure with those in the bulks,using one-shot first-principles calculations.Our calculated band offset is 0.55 eV,in comparison with 0.70 eV,obtained using other indirect methods.The obtained interface structure should prove useful for further study of the properties of CdTe/CdS heterostructures.Our work also presents an example which is applicable to other complex interfaces.

Magnetic Order and Its Interplay with Structure Phase Transition in van der Waals Ferromagnet VI_(3)

Van der Waals magnet VI_(3) demonstrates intriguing magnetic properties that render it great for use in various applications.However,its microscopic magnetic structure has not been determined yet.Here,we report neutron diffraction and susceptibility measurements in VI_(3) that revealed a ferromagnetic order with the moment direction tilted from the c-axis by ~36° at 4 K.A spin reorientation accompanied by a structure distortion within the honeycomb plane is observed,before the magnetic order completely disappears at TC=50 K.The refined magnetic moment of ~1.3μB at 4 K is much lower than the fully ordered spin moment of 2μB/V^(3+),suggesting the presence of a considerable orbital moment antiparallel to the spin moment and strong spin-orbit coupling in VI_(3).This results in strong magnetoelastic interactions that make the magnetic properties of VI_(3) easily tunable via strain and pressure.

Quantum anomalous Hall effect in real materials

Under a strong magnetic field,the quantum Hall（QH） effect can be observed in two-dimensional electronic gas systems.If the quantized Hall conductivity is acquired in a system without the need of an external magnetic field,then it will give rise to a new quantum state,the quantum anomalous Hall（QAH） state.The QAH state is a novel quantum state that is insulating in the bulk but exhibits unique conducting edge states topologically protected from backscattering and holds great potential for applications in low-power-consumption electronics.The realization of the QAH effect in real materials is of great significance.In this paper,we systematically review the theoretical proposals that have been brought forward to realize the QAH effect in various real material systems or structures,including magnetically doped topological insulators,graphene-based systems,silicene-based systems,two-dimensional organometallic frameworks,quantum wells,and functionalized Sb（111） monolayers,etc.Our paper can help our readers to quickly grasp the recent developments in this field.

An approach for full space inverse materials design by combining universal machine learning potential,universal property model,and optimization algorithm

We present a full space inverse materials design(FSIMD)approach that fully automates the materials design for target physical properties without the need to provide the atomic composition,chemical stoichiometry,and crystal structure in advance.Here,we used density functional theory reference data to train a universal machine learning potential(UPot)and transfer learning to train a universal bulk modulus model(UBmod).Both UPot and UBmod were able to cover materials systems composed of any element among 42 elements.Interfaced with optimization algorithm and enhanced sampling,the FSIMD approach is applied to find the materials with the largest cohesive energy and the largest bulk modulus,respectively.NaCl-type ZrC was found to be the material with the largest cohesive energy.For bulk modulus,diamond was identified to have the largest value.The FSIMD approach is also applied to design materials with other multi-objective properties with accuracy limited principally by the amount,reliability,and diversity of the training data.The FSIMD approach provides a new way for inverse materials design with other functional properties for practical applications.

A Possible Structure of the Al36 Cluster： Coexistence of Icosahedral and fcc-Like Structures

We study the atomic and electronic structures of the Al36 cluster using first principles total energy calculations with the local density approximation, and obtain a structure which has a HOMO-LUMO gap as large as 0.67eV, in agreement with experimental photoelectron spectroscopy. Its atomic structure is found to show the coexistence of icosahedral and fcc-based structures, which can be seen as a transition phase from icosahedral to fcc-bulk structures.