Comparative Reliability Studies and Analysis of Au,Pd-Coated Cu and Pd-Doped Cu Wire in Microelectronics Packaging

This paper compares and discusses the wearout reliability and analysis of Gold (Au), Palladium (Pd) coated Cu and Pd-doped Cu wires used in fineline Ball Grid Array (BGA) package. Intermetallic compound (IMC) thickness measurement has been carried out to estimate the coefficient of diffusion (D_o) under various aging conditions of different bonding wires. Wire pull and ball bond shear strengths have been analyzed and we found smaller variation in Pd-doped Cu wire compared to Au and Pd-doped Cu wire. Au bonds were identified to have faster IMC formation, compared to slower IMC growth of Cu. The obtained weibull slope, β of three bonding wires are greater than 1.0 and belong to wearout reliability data point. Pd-doped Cu wire exhibits larger time-to-failure and cycles-to-failure in both wearout reliability tests in Highly Accelerated Temperature and Humidity (HAST) and Temperature Cycling (TC) tests. This proves Pd-doped Cu wire has a greater potential and higher reliability margin compared to Au and Pd-coated Cu wires.     

Improving protein structure prediction using multiple sequence-based contact predictions

Although residue-residue contact maps dictate the topology of proteins, sequence-based ab initio contact predictions have been found little use in actual structure prediction due to the low accuracy. We developed a composite set of nine SVM-based contact predictors that are used in I-TASSER simulation in combination with sparse template contact restraints. When testing the strategy on 273 nonhomologous targets, remarkable improvements of I-TASSER models were observed for both easy and hard targets, with p value by Student's t test<0.00001 and 0.001, respectively. In several cases, template modeling score increases by >30%, which essentially converts "nonfoldable" targets into "foldable" ones. In CASP9, I-TASSER employed ab initio contact predictions, and generated models for 26 FM targets with a GDT-score 16% and 44% higher than the second and third best servers from other groups, respectively. These findings demonstrate a new avenue to improve the accuracy of protein structure prediction especially for free-modeling targets.     

A divide and conquer approach to fast loop modeling

We describe a fast ab initio method for modeling local segments in protein structures. The algorithm is based on a divide and conquer approach and uses a database of precalculated look-up tables, which represent a large set of possible conformations for loop segments of variable length. The target loop is recursively decomposed until the resulting conformations are small enough to be compiled analytically. The algorithm, which is not restricted to any specific loop length, generates a ranked set of loop conformations in 20-180 s on a desktop PC. The prediction quality is evaluated in terms of global RMSD. Depending on loop length the top prediction varies between 1.06 A RMSD for three-residue loops and 3.72 A RMSD for eight-residue loops. Due to its speed the method may also be useful to generate alternative starting conformations for complex simulations.     

An energetic correlation of ab initio and NMR studies of the 3'-gauche effect in 3'-substituted thymidines

A straightforward correlation of our experimental NMR findings on 3'-substituted thymidine derivatives with that of the ab initio calculations shows that (i) the delta Go298kNRM of N reversible S equilibrium in nucleoside can be predicted from the ab initio calculated delta ES-N obtained from 6-311++G** level of theory; (ii) the substituent-dependent steric and stereoelectronic effects on the bias of the two-state N reversible S equilibrium in nucleosides can also be predicted from the ab initio calculations with sufficiently large basis functions, and (iii) the necessity of mimicking the solvation behaviour of the experimental NMR measurement condition in the ab initio calculations of biomolecules is also emphasized.     

High-level ab initio calculations on the energetics of low-lying spin states of biologically relevant transition metal complexes: a first progress report

Although DFT is the unrivaled method of choice for quantum chemical studies of bioinorganic problems, little is known about its ability to predict the energetics of the low-lying electronic states of transition metal complexes. The first high-level ab initio calculations aimed at calibrating DFT vis-a-vis this issue indicate that, despite its many successes, DFT is far from infallible. In the short term, additional calibration of DFT against more elaborate ab initio methods remains an important goal for computational bioinorganic researchers. In the longer term, we are optimistic that high-level ab initio methods such as CASPT2 and CCSD(T) will be regularly used to study realistic molecules of genuine biochemical interest.     

The nature of intermolecular interactions between aromatic amino acid residues

The nature of intermolecular interactions between aromatic amino acid residues has been investigated by a combination of molecular dynamics and ab initio methods. The potential energy surface of various interacting pairs, including tryptophan, phenilalanine, and tyrosine, was scanned for determining all the relevant local minima by a combined molecular dynamics and conjugate gradient methodology with the AMBER force field. For each of these minima, single-point correlated ab initio calculations of the binding energy were performed. The agreement between empirical force field and ab initio binding energies of the minimum energy structures is excellent. Aromatic-aromatic interactions can be rationalized on the basis of electrostatic and van der Waals interactions, whereas charge transfer or polarization phenomena are small for all intermolecular complexes and, particularly, for stacked structures. Proteins 2002;48:117-125.     

Dipeptidyl alpha-fluorovinyl Michael acceptors: synthesis and activity against cysteine proteases

The synthesis of novel dipeptidyl alpha-fluorovinyl sulfones using a Horner-Wadsworth-Emmons approach on N-Boc-l-phenylalaninal is described. Inhibitory assays against a Leishmania mexicana cysteine protease (CPB2.8DeltaCTE) revealed low biological activity. Relative rates of Michael additions of 2'-(phenethyl)thiol with vinyl sulfone and alpha-fluorovinyl sulfone were determined, and ab initio calculations on several Michael acceptor model structures were performed; both were in agreement with the biological testing results.     

Prospects for ab initio protein structural genomics

We present the results of a large-scale testing of the ROSETTA method for ab initio protein structure prediction. Models were generated for two independently generated lists of small proteins (up to 150 amino acid residues), and the results were evaluated using traditional rmsd based measures and a novel measure based on the structure-based comparison of the models to the structures in the PDB using DALI. For 111 of 136 all alpha and alpha/beta proteins 50 to 150 residues in length, the method produced at least one model within 7 A rmsd of the native structure in 1000 attempts. For 60 of these proteins, the closest structure match in the PDB to at least one of the ten most frequently generated conformations was found to be structurally related (four standard deviations above background) to the native protein. These results suggest that ab initio structure prediction approaches may soon be useful for generating low resolution models and identifying distantly related proteins with similar structures and perhaps functions for these classes of proteins on the genome scale.     

Calorimetric and computational study of enthalpy of formation of 3,6-dibutanoic-1,2,4,5-tetroxane

A thermochemical a rather simple experimental technique method, is used to determine the enthalpy of the formation of 3,6-dibutanoic-1,2,4,5-tetroxane. The study is complemented with suitable theoretical calculations at the semiempirical and ab initio levels. A particular satisfactory agreement between both ways is found for the ab initio calculation at the 6-311G basis set level. Some possible extensions of the present procedure are pointed out.     

Study of nonplanarity of peptide bond using theoretical calculations

The conformational dependence of nonplanarity of the peptide bond of formylglycinamide has been studied using ab initio and density functional theory methods. Hartree-Fock self-consistent field theory (HF), M?ller-Plesset perturbation theory (MP2) of ab initio and B3LYP level of theory of dft method have been used employing 6-31++G** basis set. The MP2 method predicts better results than HF and B3LYP levels of theory for conformational stability dependence of nonplanarity. Systematic dependence of planarity deviation has been observed in MP2 theory. The chemical hardness values successfully predict the conformational region, but fail to obey maximum hardness principle. It is concluded that the most reliable dft method could not successfully predict the planarity of peptide bond in comparison with electron correlated method of ab initio method.     

The Hydrolysis Mechanism of Formamide Revisited: Comparison Between ab initio, Semiempirical and DFT Results

The hydrolysis of amides is a model reaction to study peptide hydrolysis. This process has been previously considered in the literature at the ab initio level. In this work, we revisit different reaction mechanisms (water-assisted, non-assisted, neutral and acid-catalyzed) with various theoretical methods : semiempirical, ab initio and Density Functional. The ab initio calculations are carried out at a computational level which is substantially higher than in previous studies. We describe the structure of the transition states and discuss the influence of the catalyst. We also compute the activation free energies for these processes at the Density Functional Theory level. Comparison of the methods allows to outline the main trends of these theoretical approaches which may be useful to design new computational strategies for investigating biological reaction mechanisms through the use of combined Quantum Mechanics/Molecular Mechanics methods.     

Calculation and display of electrostatic potentials

A general methodology is developed for incorporating accurate electrostatic information from ab initio molecular orbital calculations into molecular mechanics calculations. Examples are given of the method applied to simple aromatic organic molecules. A program has been developed for displaying the results of the ab initio calculations on a Silicon Graphics workstation. The technique developed here provides an alternative method for including electrostatic interactions in molecular mechanics calculations and is compared with other methods for determining atomic charges.     

蛋白质结构从头预测方法研究进展

蛋白质结构从头预测是不依赖模板仅从氨基酸序列信息得到天然结构。它的关键是正确定义能量函数、精确选用计算机搜索算法来寻找能量最低值。基于此,本文系统介绍了能量函数和构象搜索策略,并列举了几种比较成功的从头预测方法,通过比较得出结论:基于统计学知识的能量函数是近年来从头预测发展的主要方向,现有从头预测的构象搜索都用到Monte Carlo法。这表明随着蛋白质结构预测研究的深入,能量函数的构建、构象搜索方法的选择、大分子蛋白质结构的从头预测等关键性问题都取得了突破性进展。     

Structure prediction of biological assemblies using GALAXY in CAPRI rounds 38-45

We participated in CARPI rounds 38-45 both as a server predictor and a human predictor. These CAPRI rounds provided excellent opportunities for testing prediction methods for three classes of protein interactions, that is, protein-protein, protein-peptide, and protein-oligosaccharide interactions. Both template-based methods (GalaxyTBM for monomer protein, GalaxyHomomer for homo-oligomer protein, GalaxyPepDock for protein-peptide complex) and ab initio docking methods (GalaxyTongDock and GalaxyPPDock for protein oligomer, GalaxyPepDock-ab-initio for protein-peptide complex, GalaxyDock2 and Galaxy7TM for protein-oligosaccharide complex) have been tested. Template-based methods depend heavily on the availability of proper templates and template-target similarity, and template-target difference is responsible for inaccuracy of template-based models. Inaccurate template-based models could be improved by our structure refinement and loop modeling methods based on physics-based energy optimization (GalaxyRefineComplex and GalaxyLoop) for several CAPRI targets. Current ab initio docking methods require accurate protein structures as input. Small conformational changes from input structure could be accounted for by our docking methods, producing one of the best models for several CAPRI targets. However, predicting large conformational changes involving protein backbone is still challenging, and full exploration of physics-based methods for such problems is still to come.     

A multibody, whole-residue potential for protein structures, with testing by Monte Carlo simulated annealing

A new multibody, whole-residue potential for protein tertiary structure is described. The potential is based on the local environment surrounding each main-chain alpha carbon (CA), defined as the set of all residues whose CA coordinates lie within a spherical volume of set radius in 3-dimensional (3D) space surrounding that position. It is shown that the relative positions of the CAs in these local environments belong to a set of preferred templates. The templates are derived by cluster analysis of the presently available database of over 3000 protein chains (750,000 residues) having not more than 30% sequence similarity. For each template is derived also a set of residue propensities for each topological position in the template. Using lookup tables of these derived templates, it is then possible to calculate an energy for any conformation of a given protein sequence. The application of the potential to ab initio protein tertiary structure prediction is evaluated by performing Monte Carlo simulated annealing on test protein sequences.     

Conformational behavior of α,α-dialkylated peptides: Ab initio and empirical results for cyclopropylglycine

The preferred conformations of model cyclopropylglycine peptides have been investigated by means of ab initio and empirical methods. Empirical computations performed with fixed bond lengths and valence angles using two well-known force fields show that only values of ? in the ranges ±70° ± 20° are sterically allowed, and that the C₇-conformation corresponds to the absolute energy minimum irrespective of the terminal groups used. Also, ab initio computations give similar results, but suggest greater stabilities for bridge and, especially, extended structures. These discrepancies can be removed, adding to the empirical force field a twofold torsional potential on ψ and using softer steric repulsive potentials. Complete geometry optimization using both ab initio and empirical methods does not affect the relative stabilities of folded conformations, but leads to a further significant stabilization of the fully extended structure via large modifications of some valence angles.     

Comparing Associations in two Independent Fourfold Tables

A test is derived for comparing the associations in two independent fourfold tables. The test is based on the odd ratio as a measure of association but may likewise be applied for testing the difference between two phi coefficients. For small samples an exact test version is given with tables for reading critical phi differences. For large samples an asymptotic version is reported, requiring, however, the solution of a cubic equation. A typical bivariate application is illustrated, using a numerical example from psycho-pharmacology, and univariate applications are also discussed.     

Progress in protein structure prediction: assessment of CASP3.

The third comparative assessment of techniques of protein structure prediction (CASP3) was held during 1998. This is a blind trial in which structures are predicted prior to having knowledge of the coordinates, which are then revealed to enable the assessment. Three sections at the meeting evaluated different methodologies - comparative modelling, fold recognition and ab initio methods. For some, but not all of the target coordinates, high quality models were submitted in each of these sections. There have been improvements in prediction techniques since CASP2 in 1996, most notably for ab initio methods.