Enabling ab initio Hessian and frequency calculations of large molecules

A linear scaling method, termed as cardinality guided molecular tailoring approach, is applied for the estimation of the Hessian matrix and frequency calculations of spatially extended molecules. The method is put to test on a number of molecular systems largely employing the Hartree-Fock and density functional theory for a variety of basis sets. To demonstrate its ability for correlated methods, we have also performed a few test calculations at the Moller-Plesset second order perturbation theory. A comparison of central processing unit and memory requirements for medium-sized systems with those for the corresponding full ab initio computation reveals substantial gains with negligible loss of accuracy. The technique is further employed for a set of larger molecules, Hessian and frequency calculations of which are not possible on commonly available personal-computer-type hardware.Financial support from the Center for Development of Advanced Computing C-DAC, Pune, Naval Research Board NRB, New Delhi, and Council of Scientific and Industrial Research CSIR, New Delhi is gratefully acknowledged

Signatures of molecular recognition from the topography of electrostatic potential

The recognition of interaction between two molecules is analysed via the topography of their molecular electrostatic potentials (MESP). The point of recognition between two species is proposed to be the geometry at which there is a change in the nature of the set of MESP critical points of one of the molecules vis-a-vis with its MESP topography at infinite separation. These results are presented for certain model systems such as pyridine and benzene dimers, cytosine-guanine and adenine-thymine base pairs in various orientations of approach of the two species

Molecular tailoring approach for geometry optimization of large molecules: Energy evaluation and parallelization strategies

A linear-scaling scheme for estimating the electronic energy, gradients, and Hessian of a large molecule at ab initio level of theory based on fragment set cardinality is presented. With this proposition, a general, cardinality-guided molecular tailoring approach (CG-MTA) for ab initio geometry optimization of large molecules is implemented. The method employs energy gradients extracted from fragment wave functions, enabling computations otherwise impractical on PC hardware. Further, the method is readily amenable to large scale coarse-grain parallelization with minimal communication among nodes, resulting in a near-linear speedup. CG-MTA is applied for density-functional-theory-based geometry optimization of a variety of molecules including alpha-tocopherol, taxol, gamma-cyclodextrin, and two conformations of polyglycine. In the tests performed, energy and gradient estimates obtained from CG-MTA during optimization runs show an excellent agreement with those obtained from actual computation. Accuracy of the Hessian obtained employing CG-MTA provides good hope for the application of Hessian-based geometry optimization to large molecules.The authors thank C-DAC, UGC (CAS program to the University of Pune) and the Council of Scientific and Industrial Research (CSIR), New Delhi for financial assistance

Molecular tailoring approach for exploring structures, energetics and properties of clusters

Molecular Tailoring Approach (MTA) is a method developed for enabling ab initio calculations on prohibitively large molecules or atomic/molecular clusters. A brief review of MTA, a linear scaling technique based on set inclusion and exclusion principle, is provided. The Molecular Electrostatic Potential (MESP) of smaller clusters is exploited for building initial geometries for the larger ones, followed by MTA geometry optimization. The applications of MTA are illustrated with a few test cases such as (CO2)n and Lin clusters employing Density Functional theory (DFT) and a nanocluster of orthoboric acid at the Hartree-Fock (HF) level. Further, a discussion on the geometries and energetics of benzene tetramers and pentamers, treated at the Moller-Plesset second order (MP2) perturbation theory, is given. MTA model is employed for evaluating some cluster properties viz. adiabatic ionization potential, MESP, polarizability, Hessian matrix and infrared frequencies. These property evaluations are carried out on a series of test cases and are seen to offer quite good agreement with those computed by an actual calculation. These case studies highlight the advantages of MTA model calculations vis-a-vis the actual ones with reference to the CPU-time, memory requirements and accuracy

Comprehensive analysis of preeclampsia-associated DNA methylation in the placenta

Background:A small number of recent reports have suggested that altered placental DNA methylation may be associated with early onset preeclampsia. It is important that further studies be undertaken to confirm and develop these findings. We therefore undertook a systematic analysis of DNA methylation patterns in placental tissue from 24 women with preeclampsia and 24 with uncomplicated pregnancy outcome

The CD8 Antiviral Factor (CAF) can suppress HIV-1 transcription from the Long Terminal Repeat (LTR) promoter in the absence of elements upstream of the CATATAA box

Background: The CD8 Antiviral Factor (CAF) suppresses viral transcription from the HIV-1 Long Terminal Repeat (LTR) promoter in a non-cytolytic manner. However, the region on the LTR upon which CAF acts is unknown. Our objective was to determine the region on the LTR upon which CAF acts to suppress HIV-1 transcription. Methods. Serial deletions of the LTR from the 5' end and inactivating point mutations were made

A review of breast cancer awareness among women in India: cancer literate or awareness deficit?

Abstract not availableA. Gupta, K. Shridhar, P.K. Dhillo

Rotating flux-focusing eddy current probe for flaw detection

A flux-focusing electromagnetic sensor which uses a ferromagnetic flux-focusing lens simplifies inspections and increases detectability of fatigue cracks about circular fasteners and other circular inhomogeneities in high conductivity material. The unique feature of the device is the ferrous shield isolating a high-turn pick-up coil from an excitation coil, The use of the magnetic shield is shown to produce a null voltage output across the receiving coil in the presence of an unflawed sample. A redistribution of the current flow in the sample caused by the presence of flaws, however, eliminates the shielding condition and a large output voltage is produced, yielding a clear unambiguous flaw signal. By rotating the probe in a path around a circular fastener such as a rivet while maintaining a constant distance between the probe and the center of a rivet, the signal due to current flow about the rivet can be held constant. Any further changes in the current distribution, such as due to a fatigue crack at the rivet joint, can be detected as an increase in the output voltage above that due to the flow about the rivet head

Face selectivity in electrophilic additions to methylenenorsnoutanes: relative importance of through-space, through-bond and electrostatic interactions

4-Substituted 9-methylenenorsnoutanes undergo a variety of electrophilic additions with a small but consistent syn preference; ab initio MESP maps indicate that electrostatic factors and through-space interaction between the double bond and cyclopropane Walsh orbitals are unimportant in determining the face selectivity, while AM1 transition state energetics suggest that the observed preferences are determined primarily by through-bond interactions

Construction of a series of vectors for high throughput cloning and expression screening of membrane proteins from Mycobacterium tuberculosis

<p>Abstract</p> <p>Background</p> <p>One of the major challenges for membrane protein structural genomics is establishing high-throughput cloning and expression screening methods to obtain enough purified protein in a homogeneous preparation for structural and functional studies. Here a series of ligation independent cloning based vectors were constructed to address this challenge.</p> <p>Results</p> <p>The feasibility of these vectors was tested with 41 putative membrane proteins from <it>Mycobacterium tuberculosis</it>. The efficiency for direct cloning of these target genes from PCR products was 95% (39/41). Over 40% of cloned genes were overexpressed in <it>Escherichia coli </it>BL21 (DE3)-RP codon plus strain in the first round of expression screening. For those proteins which showed no expression, three protein fusion partners were prepared and it was found that each of the target proteins could be overexpressed by at least one of these fusions, resulting in the overexpression of two thirds of the cloned genes.</p> <p>Conclusion</p> <p>This expression platform features high throughput cloning, high flexibility for different constructs, and high efficiency for membrane protein overexpression, and is expected to be useful in membrane protein structural and functional studies.</p