Successive refinement of structures with data of increasing resolution: a theoretical study for triclinic space groups

The method of least squares could be used to refine an imperfectly related trial structure by adoption of one of the following two procedures: (i) using all the observed at one time or (ii) successive refinement in stages with data of increasing resolution. While the former procedure is successful in the case of trial structures which are sufficiently accurate, only the latter has been found to be successful when the mean positional error (i.e.<|[Delta]r|>) for the atoms in the trial structure is large. This paper makes a theoretical study of the variation of the R index, mean phase-angle error, etc. as a function of <|[Delta]r|> for data corresponding to different esolutions in order to find the best refinement procedure [i.e. (i) or (ii)] which could be successfully employed for refining trial structures in which <|[Delta]r|> has large, medium and low values. It is found that a trial structure for which the mean positional error is large could be refined only by the method of successive refinement with data of increasing resolution.

Photochemical, photophysical, and theoretical studies on cyclobutanethiones..alpha.-Cleavage reactions

Photophysics and photochemistry of cyclobutanethiones 1-5 have been studied with the view to generalize the a-cleavage reactions of cyclobutanethiones. The above cyclobutanethiones possess a unit intersystem crossing efficiency from S1 to T1, a high self-quenching rate (-4 X lo9 M-' s-'), and a short triplet lifetime (<0.50 ws). Photolysis of 1-5 yields in benzene a product resulting from 1,3-transposition and in methanol two cyclic thioacetals.The origin of these products is traced to the triplet excited state. A mechanistic scheme involving a-cleavage as the primary photoprocess and diradicals and thiacarbenes as intermediates has been formulated to rationalize the formation of thioacetals and rearranged products. The proposed mechanistic scheme is supported by UHF MIND013 calculations performed on four model systems, cyclobutanethiones and 1,3-cyclobutanedithiones 18-21. These calculations indicate that formation of diradical is favored thermodynamically and kinetically for systems analogous to 19 and 21, while rearrangement to thiacarbene is likely only for those similar to 21.

Formant extraction from linear-prediction phase spectra

Extraction of formant information from linear-prediction phase spectra is proposed. It is shown that the derivative of phase spectrum gives reliable formant information. Since the phase spectra for several resonators in cascade are additive, the resonance peaks are additive in the derivative of the phase spectrum unlike in the magnitude spectrum and hence the problem of identifying merged peaks is very easily solved by this method. Application of the method is illustrated through examples of linear-prediction spectra obtained for simulated models and for actural speech segments.

Prediction of Specimen Strain from Extensometer Deflection Measurements in a Direct Stress Fatigue Test Specimen under Static Tensile Loading

The displacement between the ridges situated outside the filleted test section of an axially loaded unnotched specimen is computed from the axial load and shape of the specimen and compared with extensometer deflection data obtained from experiments. The effect of prestrain on the extensometer deflection versus specimen strain curve has been studied experimentally and analytically. An analytical study shows that an increase in the slope of the stress-strain curve in the inelastic region increases the slope of the corresponding computed extensometer deflection versus specimen strain curve. A mathematical model has been developed which uses a modified length ¯ℓef in place of the actual length of the uniform diameter test section of the specimen. This model predicts the extensometer deflection within 5% of the corresponding experimental value. This method has been successfully used by the authors to evolve an iterative procedure for predicting the cyclic specimen strain in axial fatigue tests on unnotched specimens.

Structural studies of analgesics and their interactions. XII. Structure and interactions of anti-inflammatory fenamates. A concerted crystallographic and theoretical conformational study

A theoretical conformational analysis of fenamates, which are N-arylated derivatives of anthranilic acid or 2-aminonicotinic acid with different substituents on the aryl (phenyl) group, is reported. The analysis of these analgesics, which are believed to act through the inhibition of prostaglandin biosynthesis, was carried out using semi-empirical potential functions. The results and available crystallographic observations have been critically examined in terms of their relevance to drug action. Crystallographic studies of these drugs and their complexes have revealed that the fenamate molecules share a striking invariant feature, namely, the sixmembered ring bearing the carboxyl group is coplanar with the carboxyl group and the bridging imino group,the coplanarity being stabilized by resonance interactions and an internal hydrogen bond between the imino and carboxyl groups. The results of the theoretical analysis provide a conformational rationale for the observed invariant coplanarity. The second sixmembered ring, which provides hydrophobicity in a substantial part of the molecule, has limited conformational flexibility in meclofenamic, mefenamic and flufenamic acids. Comparison of the conformational energy maps of these acids shows that they could all assume the same conformation when bound to the relevant enzyme. The present study provides a structural explanation for the difference in the activity of niflumic acid, which can assume a conformation in which the whole molecule is nearly planar. The main role of the carboxyl group appears to be to provide a site for intermolecular interactions in addition to helping in stabilizing the invariant coplanar feature and providing hydrophilicity at one end of the molecule. The fenamates thus provide a good example of conformation- dependent molecular asymmetry.

Theoretical studies on alpha-helix--DNA interactions

The interaction energies between (Ala)10 and alpha-helix fragment and different nucleotide sequences in right-handed B-form have been optimized using semi-empirical potential energy functions. The energies are calculated for two different orientations of the alpha-helix, viz., when the alpha-helix axis taken in the N----C direction is (i) parallel and (ii) antiparallel to the 5'-3' ascending strand of DNA, proximal to it. When both the DNA molecule as well as the alpha-helix are treated as rigid molecules it is found that a polyalanine alpha-helix has slightly more favourable contacts when it is in the proximity of a four nucleotide sequence of 5'-(N-A-T-N)-3' type, where N is either a purine or a pyrimidine. However, when the two interacting molecules are allowed to undergo local structural variations then the interaction energy appears to be independent of the base sequence confirming the non-specific nature of these interactions.

Kalman Filter Algorithm for Rating and Prediction in Basketball

The Thesis presents a state-space model for a basketball league and a Kalman filter algorithm for the estimation of the state of the league. In the state-space model, each of the basketball teams is associated with a rating that represents its strength compared to the other teams. The ratings are assumed to evolve in time following a stochastic process with independent Gaussian increments. The estimation of the team ratings is based on the observed game scores that are assumed to depend linearly on the true strengths of the teams and independent Gaussian noise. The team ratings are estimated using a recursive Kalman filter algorithm that produces least squares optimal estimates for the team strengths and predictions for the scores of the future games. Additionally, if the Gaussianity assumption holds, the predictions given by the Kalman filter maximize the likelihood of the observed scores. The team ratings allow probabilistic inference about the ranking of the teams and their relative strengths as well as about the teams’ winning probabilities in future games. The predictions about the winners of the games are correct 65-70% of the time. The team ratings explain 16% of the random variation observed in the game scores. Furthermore, the winning probabilities given by the model are concurrent with the observed scores. The state-space model includes four independent parameters that involve the variances of noise terms and the home court advantage observed in the scores. The Thesis presents the estimation of these parameters using the maximum likelihood method as well as using other techniques. The Thesis also gives various example analyses related to the American professional basketball league, i.e., National Basketball Association (NBA), and regular seasons played in year 2005 through 2010. Additionally, the season 2009-2010 is discussed in full detail, including the playoffs.

Theoretical and Experimental Studies on an Ammonia-Based Loop Heat Pipe With a Flat Evaporator

An ammonia loop heat pipe (LHP) with a flat plate evaporator is developed and tested. The device uses a nickel wick encased in an aluminum-stainless steel casing. The loop is tested for various heat loads and different sink temperatures, and it demonstrated reliable startup characteristics. Results with the analysis of the experimental observation indicate that the conductance between the compensation chamber and the heater plate can significantly influence the operating temperatures of the LHP. A mathematical model is also presented which is validated against the experimental observations.

Prediction of protein-protein interactions in dengue virus coat proteins guided by low resolution cryoEM structures

Background: Dengue virus along with the other members of the flaviviridae family has reemerged as deadly human pathogens. Understanding the mechanistic details of these infections can be highly rewarding in developing effective antivirals. During maturation of the virus inside the host cell, the coat proteins E and M undergo conformational changes, altering the morphology of the viral coat. However, due to low resolution nature of the available 3-D structures of viral assemblies, the atomic details of these changes are still elusive. Results: In the present analysis, starting from C alpha positions of low resolution cryo electron microscopic structures the residue level details of protein-protein interaction interfaces of dengue virus coat proteins have been predicted. By comparing the preexisting structures of virus in different phases of life cycle, the changes taking place in these predicted protein-protein interaction interfaces were followed as a function of maturation process of the virus. Besides changing the current notion about the presence of only homodimers in the mature viral coat, the present analysis indicated presence of a proline-rich motif at the protein-protein interaction interface of the coat protein. Investigating the conservation status of these seemingly functionally crucial residues across other members of flaviviridae family enabled dissecting common mechanisms used for infections by these viruses. Conclusions: Thus, using computational approach the present analysis has provided better insights into the preexisting low resolution structures of virus assemblies, the findings of which can be made use of in designing effective antivirals against these deadly human pathogens.

Stereochemically constrained peptides. Theoretical and experimental studies on the conformations of peptides containing 1-aminocyclohexane carboxylic acid

Conformational energy calculations on the model system N-acetyl- 1 -aminocyclohexanecarboxylic acid N'methylamide (Ac-Acc6-NHMe), using an average geometry derived from 13 crystallographic observations, establish that the Acc6 residue is constrained to adopt conformations in the helical regions of In contrast, the a,a-dialkylated residue with linear hydrocarbon side chains, a,a-di-n-propylglycine favors fully extended backbone structures (6 1= $ = 180'). The crystal structures of two model peptides, Boc-(Acc6),-OMe (type 111 @-turn at -Acc6(1)-Acc6(2)-) and Boc-Pro-Acc6-Ala-OMe (type I1 P-turn at -Pro-Acc6-), establish that Acc6 residues can occupy either position of type 111 P-turns and the i + 2 position of type I1 @-turns. The stereochemical rigidity of these peptides is demonstrated in solution by NMR studies, which establish the presence of one intramolecular hydrogen bond in each peptide in CDCI, and (CDJ2S0. Nuclear Overhauser effects permit characterization of the @-turn conformations in solution and establish their similarity to the solid-state structures. The implications for the use of Acc6 residues in conformational design are considered.

Use of 2-pyrimidineamidoxime to generate polynuclear homo-/heterometallic assemblies: synthesis, crystal structures and magnetic study with theoretical investigations on the exchange mechanism

Three new transition metal complexes using 2-pyrimidineamidoxime (pmadH(2)) as multidentate chelating and/or bridging ligand have been synthesized and characterized. The ligand pmadH(2) has two potential bridging functional groups mu-O and mu-(N-O)] and consequently shows several coordination modes. While a polymeric 1D Cu-II complex Cu(pmadH(2))(2)(NO3)](NO3) (1) was obtained upon treatment of Cu(NO3)(2)center dot 3H(2)O with pmadH(2) at room temperature in the absence of base, a high temperature reaction in the presence of base yielded a tetranuclear Cu-II-complex Cu-4(pmad)(2)(pmadH)(2)(NO3)](NO3)(H2O) (2). One of the Cu-II centers is in a square pyramidal environment while the other three are in a square planar geometry. Reaction of the same ligand with an equimolar mixture of both Cu(NO3)(2)center dot 3H(2)O and NiCl2 center dot 6H(2)O yielded a tetranuclear heterometallic (Cu2Ni2II)-Ni-II complex Cu2Ni2(pmad)(2)(pmadH)(2)Cl-2]center dot H2O (3) containing both square planar (Ni-II) and square pyramidal (Cu-II) metal centers. Complexes 1-3 represent the first examples of polynuclear metal complexes of 2-pyrimidineamidoxime. The analysis of variable temperature magnetic susceptibility data of 2 reveals that both ferromagnetic and antiferromagnetic interactions exist in this complex (J(1) = +10.7 cm(-1) and J(2) = -2.7 cm(-1) with g = 2.1) leading to a resultant ferromagnetic behavior. Complex 3 shows expected antiferromagnetic interaction between two Cu-II centers through -N-O- bridging pathway with J(1) = -3.4 cm(-1) and g = 2.08. DFT calculations have been used to corroborate the magnetic results.