Ab Initio Program Research Articles

Identification of the nature of reading frame transitions observed in prokaryotic genomes

Our goal was to identify evolutionary conserved frame transitions in protein coding regions and to uncover an underlying functional role of these structural aberrations. We used the ab initio frameshift prediction program, GeneTack, to detect reading frame transitions in 206 991 genes (fs-genes) from 1106 complete prokaryotic genomes. We grouped 102 731 fs-genes into 19 430 clusters based on sequence similarity between protein products (fs-proteins) as well as conservation of predicted position of the frameshift and its direction. We identified 4010 pseudogene clusters and 146 clusters of fs-genes apparently using recoding (local deviation from using standard genetic code) due to possessing specific sequence motifs near frameshift positions. Particularly interesting was finding of a novel type of organization of the dnaX gene, where recoding is required for synthesis of the longer subunit, τ. We selected 20 clusters of predicted recoding candidates and designed a series of genetic constructs with a reporter gene or affinity tag whose expression would require a frameshift event. Expression of the constructs in Escherichia coli demonstrated enrichment of the set of candidates with sequences that trigger genuine programmed ribosomal frameshifting; we have experimentally confirmed four new families of programmed frameshifts.

Theoretical studies of electronic structure and structural properties of anhydrous alkali metal oxalates

The results of first principles calculations of band structure, density of states, and electron density topology of alkali metal oxalates are presented. The calculations have been carried out with WIEN2k ab initio program, using highly precise full potential linearized augmented plane wave method within density functional theory formalism. Calculated total electron density has been used in calculations of its topological properties (according to Bader’s quantum theory of atoms in molecules formalism) and Cioslowski and Mixon’s topological bond orders. The obtained results show important similarities between electronic structure and electron density topology for all analyzed structures with electronic structure close to Fermi energy typical for ionic compounds and bonding which is mainly covalent within the oxalate anion (with partly ionic character of carbon–oxygen bonds) and strongly ionic between oxalate anion and cationic sublattice. These results have been used as a basis for theoretical analysis of thermal decomposition process described in detail in part II of this paper (where also the results of additional calculations of atomic and bond valences, bond strengths and strains are presented).

What is Wrong with Quantitative Structure–Property Relations Models Based on Three-Dimensional Descriptors?

Quantitative structure-property relations (QSPR) employing descriptors derived from the three-dimensional (3D) molecular structure are frequently applied for property prediction in various fields of research. However, there is no common understanding of the necessary degree of detail to which molecular structure has to be known for reliable descriptor evaluation, but computational methods used vary from simplified molecular mechanics up to rigorous ab initio programs. In order to quantify the yet unknown error due to this heterogeneity, widely used 3D molecular descriptors from diverse fields of application are evaluated for molecular structures computed by different computational methods. The results clearly indicate that the widespread, exclusive use of the most stable molecular conformation as well as too simplistic computational methods yield systematically erroneous descriptor values with misleading information for the inferred structure-property relations. Thus, generating an awareness and understanding of this fundamental problem is considered an important first step to make 3D QSPR a generally accepted property prediction method.

Improved annotation of a plant pathogen genome Xanthomonas oryzae pv. oryzae PXO99A

Many bacterial genomes have been sequenced and stored in public databases now, of which Reference Sequence (RefSeq) is the most widely used one. However, the annotation in RefSeq is still unsatisfactory. The present analysis is focused on the re-annotation of an important plant pathogen genome Xanthomonas oryzae pv. oryzae PXO99A (Xoo PXO99A), which is the causal agent of bacterial blight on rice. Based on the parameters of 28 nucleotide frequencies and support vector machine algorithm, 41 originally annotated hypothetical genes were recognized as noncoding sequences, which were further supported by principal component analysis and other evidence. Ten of them were tested with reverse transcription-polymerase chain reaction experiments (RT-PCR), and all of them were confirmed to be noncoding sequences. Furthermore, 197 potential new genes not annotated in RefSeq were both recognized by two ab initio gene finding programs. Most of them only have sequence similarities with part of the known genes in other species, so they are unlikely to be protein-coding genes. Twelve potential new genes have high full-length sequence similarities with function-known genes, which are very likely to be true protein-coding genes. All the 12 potential genes were tested with RT-PCR, and 11 of them (92%) were successfully amplified in cDNA template. The RT-PCR experiments confirm that our theoretical prediction has high accuracy. The improvement of Xoo PXO99A annotation is helpful for the research of lifestyle, metabolism, and pathogenicity of this important plant pathogen. The improved annotation can be obtained from http://211.69.128.148/Xoo.

Theoretical investigation of the effect of sugar substitution on the antioxidant properties of flavonoids

Natural flavonoids are secondary phenolic plant metabolites known for their bioactivity as antioxidants. The evaluation of this property is generally done by the estimation of their direct free radical-scavenging activity as hydrogen or electron donating compounds. This paper reviews experimental results available in the literature for a selection of flavonoids and compares them with calculated quantities characteristic of the hydrogen or electron donation. For that purpose, bond dissociation energies, ionization potentials and electron transfer enthalpies are computed by using DFT methods and the ONIOM procedure implemented in the ab initio program Gaussian. This process has been chosen because it can be extended to the study of large molecules. When acid dissociation and interaction with the solvent are taken into account, the results present very good concordance with experimental results, enlightening the complexity of the processes involved in the classical assays which measure the ability of compounds to scavenge the (2,2′-azinobis-(3-ethylbenzthiazoline-6-sulfonic acid) diammonium salt) radical cation (ABTS +) or the 2,2-diphenyl-1-picryl-hydrazyl radical (DPPH·). This study demonstrates the good accuracy of theoretical calculations in obtaining the relative energies involved in free radical scavenging abilities and its capacity for predictive behaviour. It also highlights the necessity to take into account the pKa of the compounds and the solvent interaction. The ability of the method to calculate the antioxidant properties of larger molecules are tested on glycosylated flavonoids and the effects of sugar substitution on the antioxidant properties of flavonoids are investigated, pointing out the importance of the charges on the oxygen atoms.

Analysis of some conventional ab initio gene finders using human and mouse DNA sequences

An evaluation of the prediction accuracy of five ab initio gene prediction programs (that is, FGENESH, Genscan, HMMgene, GeneMark.hmm and FGENES) was conducted by the use of 110 human and mouse orthologous sequences. As expected, all programs presented different predictions with various ranges of accuracy. According to our results, FGENESH and Genscan generally had the maximum power to produce more reliable results in both nucleotide and exon levels than others. Although, both FGENES and GenMark.hmm predicted the highest number of exons (966 and 946 exons, respectively), when exon sensitivity ( ESn ), exon specificity ( ESp ) and ( ESn +ESp /2) were considered, their overall accurate performance descended and was clustered in the lowest positions. It was also determined that all programs have lower power in predicting initial and terminal exons, as compared to internal exons, which suggested that such programs cannot accurately determine translational start sites (TSS) and translational stop codons (TSC) as internal exons, whose boundaries are highlighted by acceptor and donor sites. Apart from the species difference, it was finally recognized that the programs, FGENESH and GeneMark.hmm, presented much more sensitivity in detecting genes with low guanine-cytosine (GC) content.

Electric dipole transition moments and permanent dipole moments for spin–orbit configuration interaction wave functions

A procedure for calculating electric dipole transition moments and permanent dipole moments from spin–orbit configuration interaction (SOCI) wave functions has been developed in the context of the COLUMBUS ab initio electronic structure programs. The SOCI procedure requires relativistic effective core potentials and their corresponding spin–orbit coupling operators to define the molecular Hamiltonian, electric dipole transition moment and permanent dipole moment matrices. The procedure can be used for any molecular system for which the COLUMBUS SOCI circuits are applicable. Example applications are reported for transition moments and dipole moments for a series of electronic states of LiBe and LiSr defined in diatomic relativistic ωω-coupling.

Wannier functions approach to van der Waals interactions in ABINIT

The method to calculate van der Waals interactions based on maximally localized Wannier functions (MLWFs), proposed by Silvestrelli [Phys. Rev. Lett. 100 (2008) 053002], has been implemented within the ab initio DFT program ABINIT. In addition to a brief review of the theoretical background behind this methodology, we present the details of the implementation, which will help users to assess van der Waals corrections in both molecular and periodic systems with a negligible additional computational cost. Some tests on argon dimer, argon FCC solid, benzene dimer and bilayer of graphene are presented. A discussion about the reliability of the method is also included.

Theoretical Study on Photochromism and Spectrum Properties of Spiropyran

In order to elucidate the mechanism of photochromism and spectrum properties observed for spiropyran, the model complexes of spiropyran, in which different substituent and structure are key factors, have been optimized by using ab initio and hybrid DFT programs. The primary relationship between the substituent species and structure and photochromism was given by simulation calculation.

Next Generation Sequencing Provides Rapid Access to the Genome of Puccinia striiformis f. sp. tritici, the Causal Agent of Wheat Stripe Rust

The wheat stripe rust fungus (Puccinia striiformis f. sp. tritici, PST) is responsible for significant yield losses in wheat production worldwide. In spite of its economic importance, the PST genomic sequence is not currently available. Fortunately Next Generation Sequencing (NGS) has radically improved sequencing speed and efficiency with a great reduction in costs compared to traditional sequencing technologies. We used Illumina sequencing to rapidly access the genomic sequence of the highly virulent PST race 130 (PST-130). We obtained nearly 80 million high quality paired-end reads (>50x coverage) that were assembled into 29,178 contigs (64.8 Mb), which provide an estimated coverage of at least 88% of the PST genes and are available through GenBank. Extensive micro-synteny with the Puccinia graminis f. sp. tritici (PGTG) genome and high sequence similarity with annotated PGTG genes support the quality of the PST-130 contigs. We characterized the transposable elements present in the PST-130 contigs and using an ab initio gene prediction program we identified and tentatively annotated 22,815 putative coding sequences. We provide examples on the use of comparative approaches to improve gene annotation for both PST and PGTG and to identify candidate effectors. Finally, the assembled contigs provided an inventory of PST repetitive elements, which were annotated and deposited in Repbase. The assembly of the PST-130 genome and the predicted proteins provide useful resources to rapidly identify and clone PST genes and their regulatory regions. Although the automatic gene prediction has limitations, we show that a comparative genomics approach using multiple rust species can greatly improve the quality of gene annotation in these species. The PST-130 sequence will also be useful for comparative studies within PST as more races are sequenced. This study illustrates the power of NGS for rapid and efficient access to genomic sequence in non-model organisms.

Prediction of crystal structure, lattice dynamical, and mechanical properties of CaB 2H 2

The phase stability of CaB 2H 2 phase at ambient and high pressures was investigated using the state-of-the-art ab initio program based on density functional theory. At ambient conditions CaB 2H 2 crystallizes in orthorhombic phase (α-modification; space group Cmc21) and at high pressure it transforms into trigonal structure (β-modification; space group P 3 ¯ m1). From the lattice dynamics simulation and mechanical properties study we have found that the predicted phases are dynamically as well as mechanically stable. The chemical bonding in CaB 2H 2 is discussed on the basis of electronic structures, charge density, and bond overlap population analysis. In order to verify the possible existence of this compound experimentally we have simulated the Raman, IR spectra and NMR related parameters like isotropic chemical shielding, quadrupolar coupling constant, and quadrupolar asymmetry parameters. The electronic structures reveal that α- and β-CaB 2H 2 modifications are indirect band gap semiconductor with estimated band gap vary between 0.32 and 1.98 eV.

ANALYZING MODULAR RNA STRUCTURE REVEALS LOW GLOBAL STRUCTURAL ENTROPY IN MICRORNA SEQUENCE

Secondary structure remains the most exploitable feature for noncoding RNA (ncRNA) gene finding in genomes. However, methods based on secondary structure prediction may generate superfluous amount of candidates for validation and have yet to deliver the desired performance that can complement experimental efforts in ncRNA gene finding. This paper investigates a novel method, unpaired structural entropy (USE) as a measurement for the structure fold stability of ncRNAs. USE proves to be effective in identifying from the genome background a class of ncRNAs, such as precursor microRNAs (pre-miRNAs) that contains a long stem hairpin loop. USE correlates well and performs better than other measures on pre-miRNAs, including the previously formulated structural entropy. As an SVM classifier, USE outperforms existing pre-miRNA classifiers. A long stem hairpin loop is common for a number of other functional RNAs including introns splicing hairpins loops and intrinsic termination hairpin loops. We believe USE can be further applied in developing ab initio prediction programs for a larger class of ncRNAs.

Characterizing Intrinsically Disordered Proteins by Small-Angle Neutron Scattering

Intrinsically disordered proteins (IDPs) that undergo a coupled folding and binding event are found to be important in many recognition and signaling processes. However, exactly how this mechanism is linked to these functions is not completely understood. This is primarily because the structural flexibility of IDPs limits the number of suitable characterization techniques. We are using small-angle neutron scattering (SANS) to investigate the structure and binding interaction properties between NCBD, an IDP region of CREB binding protein (CBP), and its binding partner, ACTR, which also is an IDP. CBP is a transcription co-activator that is essential in embryonic development, growth control, and homeostasis, and its dysfunction is implicated in neurological disorders such as Huntington's disease and some cancers. SANS indicates the NCBD/ACTR complex is a globular, folded structure with a smaller radius of gyration compared to ACTR alone, which is mostly unfolded. Using ab initio shape reconstruction programs to gain further insight into structural flexibility, we find good agreement between the shape reconstruction and NMR structure for the NCBD/ACTR complex. In contrast, SANS reveals the nature of how ACTR is more expanded when in its unbound, unfolded state. This research should provide new possibilities for the study of disordered protein regions and yield unique perspectives into the mechanism of IDP function.

Efficient Plant Gene Identification Based on Interspecies Mapping of Full-Length cDNAs

We present an annotation pipeline that accurately predicts exon–intron structures and protein-coding sequences (CDSs) on the basis of full-length cDNAs (FLcDNAs). This annotation pipeline was used to identify genes in 10 plant genomes. In particular, we show that interspecies mapping of FLcDNAs to genomes is of great value in fully utilizing FLcDNA resources whose availability is limited to several species. Because low sequence conservation at 5′- and 3′-ends of FLcDNAs between different species tends to result in truncated CDSs, we developed an improved algorithm to identify complete CDSs by the extension of both ends of truncated CDSs. Interspecies mapping of 71 801 monocot FLcDNAs to the Oryza sativa genome led to the detection of 22 142 protein-coding regions. Moreover, in comparing two mapping programs and three ab initio prediction programs, we found that our pipeline was more capable of identifying complete CDSs. As demonstrated by monocot interspecies mapping, in which nucleotide identity between FLcDNAs and the genome was ∼80%, the resultant inferred CDSs were sufficiently accurate. Finally, we applied both inter- and intraspecies mapping to 10 monocot and dicot genomes and identified genes in 210 551 loci. Interspecies mapping of FLcDNAs is expected to effectively predict genes and CDSs in newly sequenced genomes.

Updated Branching Plane for Finding Conical Intersections without Coupling Derivative Vectors.

The conical intersections (CIs) form a (f-2)-dimensional hyperspace on which two diabatic potential energy surfaces (PESs) belonging to the same symmetry cross, where f is the internal degree of freedom. The branching plane (BP) is a (two-dimensional) plane defined by the difference gradient vector (DGV) and the coupling derivative vector (CDV), and on the BP, the degeneracy of the two adiabatic PESs is lifted. The properties of the BP are often used in the exploration of the conical intersection hyperspace, such as determination of the minimum energy CI or the first-order saddle point in CI. Although both DGV and CDV are necessary to construct the BP in general, CDV is not always available depending on ab initio methods and programs. Therefore, we developed an approach for optimizing critical points on the CI hypersurface without CDV by using a BP updating method, which was shown to be accurate and very useful for minimum energy and saddle point optimization and for the minimum energy path following within the CI hypersurface in numerical tests for C6H6 and C5H8N(+).

DIGAP - a Database of Improved Gene Annotation for Phytopathogens

BackgroundBacterial plant pathogens are very harmful to their host plants, which can cause devastating agricultural losses in the world. With the development of microbial genome sequencing, many strains of phytopathogens have been sequenced. However, some misannotations exist in these phytopathogen genomes. Our objective is to improve these annotations and store them in a central database DIGAP.DescriptionDIGAP includes the following improved information on phytopathogen genomes. (i) All the 'hypothetical proteins' were checked, and non-coding ORFs recognized by the Z curve method were removed. (ii) The translation initiation sites (TISs) of 20% ~ 25% of all the protein-coding genes have been corrected based on the NCBI RefSeq, ProTISA database and an ab initio program, GS-Finder. (iii) Potential functions of about 10% 'hypothetical proteins' have been predicted using sequence alignment tools. (iv) Two theoretical gene expression indices, the codon adaptation index (CAI) and the E(g) index, were calculated to predict the gene expression levels. (v) Potential agricultural bactericide targets and their homology-modeled 3D structures are provided in the database, which is of significance for agricultural antibiotic discovery.ConclusionThe results in DIGAP provide useful information for understanding the pathogenetic mechanisms of phytopathogens and for finding agricultural bactericides. DIGAP is freely available at http://ibi.hzau.edu.cn/digap/.

Can We Predict Risk-Taking Behavior?

Objective behavioral personality measures are an alternative to traditional self-report personality assessment and overcome some of the difficulties traditional assessment has. This paper presents two studies to validate two measures of risk propensity. In Study 1, 1,325 applicants for an ab initio air-traffic control training program were assessed using the Roulette Test (RT) and the Crossing the Street Test (CtST). Convergent as well as criterion validity were tested using the guessing tendency demonstrated by participants in a multiple-choice test. Once the effect of general cognitive ability was leveled out, results showed the predictive capacity of both tests. Study 2 replicated the previous study: 127 3rd-year psychology students were assessed using the RT. Results showed that the test had an even higher predictive validity of the Guessing Tendency (GT) revealed in a multiple-choice test. The usefulness for personnel recruitment processes and other assessment contexts is emphasized as are future trends of objective personality assessment.

A density-division embedding potential inversion technique

A new method is proposed to partition the density of a system in two portions. The density on each subsystem is the solution of a Fock equation modified by the addition of an embedding potential. This embedding potential is obtained iteratively by minimizing the difference between the electronic densities of the total system and the sum of the subsystems. Thus, the electronic density partition and the embedding potential are obtained at the same time within the procedure, guaranteeing the v-representability of the densities partitioned. This fact is a considerable improvement of a recently proposed embedding potential inversion technique, [O. Roncero, M. P. de Lara-Castells, P. Villarreal, F. Flores, J. Ortega, M. Paniagua, and A. Aguado, J. Chem. Phys. 129, 184104 (2008)], in which the embedding potential is obtained once the electronic density is previously partitioned. The method is first applied to a linear H(10) chain to illustrate how it works. The orbitals obtained are localized on each subsystem, and can be used to include local electronic correlation with currently available ab initio programs. Finally, the method is applied to include the electronic correlation needed to describe the van der Waals interaction between H(10) chains and H(2) molecules, of approximately 12 meV, giving very accurate results.

Structural and electronic properties of protein/thiolate-protected gold nanocluster with “staple” motif: A XAS, L-DOS, and XPS study

Following the recent breakthrough of total structural determination of a Au-thiolate nanocluster [P. Jadzinsky et al., Science 318, 430 (2007)], extensive interests have been stimulated to unveil (or revisit) the structure-property relationship of various thiolate-Au nanostructures in light of the new finding of -SR-(Au-SR)(x)- "staple" motif. Here, we present experimental x-ray absorption spectroscopy (XAS) and x-ray photoelectron spectroscopy (XPS) results on the local structure and electronic properties of thiolate-protected Au nanocluster encapsulated in bovine serum albumin (Au-BSA) together with theoretical calculation of projected local density of states (l-DOS) of Au(25)(SR)(18) model cluster. Analysis of the Au L(3)-edge extended x-ray absorption fine structure (EXAFS) of Au-BSA suggested that the nanocluster is Au(25) with Au-thiolate "staple" motif. X-ray absorption near-edge structure (XANES) and Au 4f XPS were used to probe the electronic behavior of Au-BSA. The Au d-electron density of Au-BSA was found to decrease by 0.047 e(-) relative to that of the bulk. A self-consistent real space Green's function approach implemented in ab initio FEFF8 program was used to calculate the l-DOS of Au(25)(SR)(18) and other model clusters from a site-specific perspective. The theoretical results are in good agreement with the experimental d-DOS data of Au-BSA and, importantly, systematically illustrate the effect of Au-thiolate "staple" motif on the electronic behavior of Au(25)(SR)(18). The present work sheds light on the structure-property relationship of thiolate-protected Au(25) from both experimental and theoretical perspectives and illustrates the usefulness of XAS/l-DOS method in such studies.

Ab Initio MODPOT/VRDDO/MERGE calculations on energetic compounds. II. Nitroexplosives: RDX and α-, β- and δ-HMX

Ab initio MODPOT/VRDDO calculations have been carried out on RDX and α-,β-, and δ-HMX using our ab initio programs that incorporate several desirable options for calculations on large molecules. Among these are ab initio effective core model potentials (MODPOT) that permit calculations of valence electrons only explicitly, yet accurately, and a charge-conserving integral prescreening evaluation (which we named VRDDO—variable retention of diatomic differential overlap) that is especially effective for spatially extended molecules. The resultant theoretical indices are relevant to a number of properties and behaviorial characteristics of these molecules, both intra- and intermolecular. The charges on the atoms (from the gross atomic populations) are needed for calculation of the atomic multipole-atomic multipole electrostatic contributions (a major or dominant factor) to the intermolecular interaction energies. These electrostatic interaction energies are part of the input necessary for calculations on crystal packing and densities of these molecules. The total overlap populations between atoms are related to the inherent bond strengths, which are of interest in predicting and tracing initiating steps of explosive phenomena. The molecular orbital energies of the lowest unoccupied orbitals are of particular interest since these nitroexplosives have been implicated in testicular toxicity and the initial metabolic activation appears to proceed through a one-electron reduction of the nitroexplosive.