Abstract

Identification of base pairs which can participate, through multimodality of edge interactions, in conformational switching events, and evaluation of possible environmental factors responsible for the switching can lead to greater understanding of RNA functional dynamics. Moleculardynamics studies by Schneider et al involving multimodality in C:U W:W cis interactions in aqueous medium, arguments forwarded by Van Dongen et al in support of a pH dependent G:C W:W cis to G:C H:W cis conformational switch and the postulation of putative role of a minor motifs in ribosomal dynamics through structure analysis, are examples of efforts in this section. Here we discuss the computational analysis of a putative pH dependant conformational switching of G:G base pairs in RNA structures.

Abstract

Hoogsteen-sugar base pattern of RNA base pairing is studied using density functional theory. Hydrogen bonding patterns of these base apirs are characterized using NBO analysis and AIM analysis. Correlation between strenghth of base pairing and nature of donor-acceptor combinations is also carried out.

Abstract

The backbone conformation of amino acids in proteins is represented mainly by two torsion angles; phi and psi. Ramachandran map is a way to visualize these torsion angles in protein structures. Here we analyze the nature and distribution of disallowed Ramachandran conformations of amino acid residues observed in protein structures. A non redundant data set consisting of 405 high resolution protein crystal structures from the Brookhaven Protein Data Bank was examined. The data set consisted of a total of 78,213 non-Gly residues, which were characterized on the basis of their backbone dihedral angles phi and psi. Residues falling outside the defined "broad allowed limits" on the Ramachandran map were analyzed. The results suggested that very small fraction of residues (approximately 0.4%) lie in appreciably disallowed regions. Interestingly, small polar/charged residues showed significantly greater probability of adopting unusual backbone with the largest number of examples being observed for Asn, Asp, Ser and Thr residues. The bulky charged residues Glu, Lys, Gln and Arg have a relatively low propensity for backbone distortions. Bulky hydrophobic residues which are found predominantly in well packed interiors of proteins like Ile, Val and aromatic amino acids like Phe, Trp and Tyr do not generally adopt disallowed conformations. In the allowed region irrespective of the type of amino acid except Gly, there is a high propensity for phi value of the range -70 to -60 and for psi value 140 to 150.

Abstract

With availability of fast computers, electronic structure and properties calculations of small to medium sized systems using quantum chemical methods are now commonplace. Several options in addition to obtaining structures with energy optimisation are now easily realisable, e.g., carrying out calculations of electrostatic potential interations, atoms in molecule approach of Bader, Natural Bonding orbital method, etc. We discuss results obtained in specific cases using these options. We have recently carried out studies on several such systems including amino-methyl furan carboxylic acid system and binding of gold nanoclusters with size expanded DNA bases, xA, xC, xG, and xT. We will present the motivation behind such works and discuss the results obtained using different methods. Geometries of these molecular systems were fully optimized using the Hartree Fock SCF method and using B3LYP density functional method (DFT). The calculations provide a theoretical understanding beyond a phenomenological observation of the preferential cyclotrimerization of 5- (aminomethyl)-2-furancarboxylic acid (AMFC). Other than calculations of thermodynamic free energy, a detailed analysis of the molecular properties is carried out. The electrostatic potentials (ESP) in the region around molecular skeletons are investigated to provide justication for the preferential formation of the cyclic tripeptide over the cyclic dipeptide from the building block, AMFC. The ESP are calculated and computed on the molecular surfaces of the oligopeptides. There are repulsions observed in the dimer due to the proximity of the ethereal oxygen atoms of the furan rings. Natural bond orbital (NBO) analysis is done to find the second-order interactions, and atoms in molecules (AIM) calculations are performed to explore the interactions between the donor and acceptor moieties in the molecule. Our results on the gold complexed x-bases show that the gold clusters around xA and xT adopt triangular geometries, whereas irregular structures are obtained in the case of gold clusters complexed around xC and xG. The lengths of the bonds between atoms in the x-bases increase on gold complexation. The aromaticcharacter of the x-bases also increases on gold complexation except for the five member rings. A significant charge transfer from the x-base to gold atoms is seen in these complexes. Second-order interactions are observed in addition to direct covalent bonds between gold atoms and x bases.

Abstract

The problem of predicting the 3D native conformation of a polypeptide given the primary sequence is of fundamental importance in contemporary biology. Here we present a novel Genetic algorithm method to obtain the optimal geometry of a pentapeptide. The pentapeptide moiety is found in wide set of configurations in protein databases. A genetic algorithm utilizes optimization procedure similar to natural genetic evolution. Unlike other genetic algorithms, which are constrained to operate on bit strings, the algorithm used here operates on real values. A random population of conformations is generated taking into account the constraints of Ramachandran plot. This population advances through successive generations in which the solutions evolve via genetic operators (Mutate, Variate and Crossover); in such a way that it gives both better survival chance to fitter soluctions and a larger diversity within the population. More attention will be given to favorable local structures while unfavorable local structures will be rapidly abandoned on the basis of their fitness functions (potential energy), which are calculated using the GROMOS-96 force field of Spdbv version-3.7. The SCWRL3.0 program developed at Dunbrack lab is used for placing side chains to a fixed backbone coordinates. This algorithm proved to be very efficient for the penta-peptide Met-Enkephalin, a natural Opioid polypeptide produced in the brain. The algorithm converged only in 41 minutes and in 23 generations keeping the population size fixed (20 individual per population). The converged structure is energetically as stable as the native conformation of the protein. Its shows a RMSD of 5.9 from the original native conformation.

Abstract

Controlling dynamics at the atomic level is a primary goal of chemists. In the last decade, Optimal control theory (OCT) has emerged as one comprehensive means of designing laser pulses for achieving prescribed dynamical goals. We have used OCT to obtain infrared laser pulses for the selective vibrational excitation of several different systems, from a simple diatomic to triatomic systems located in complex molecular environments. We will present our results obtained for the diatomic system HF applying OCT using different algorithmic methods, namely an iterative method, conjugate gradient method and genetic algorithms. The results of a new dynamic method for applying the penalty term needed to keep the power in the electric field of the laser within reasonable bounds will be discussed. For the triatomic FeCO, we use a two mathematical dimensional model of carboxy-myoglobin. Density functional theory is used to obtain the potential energy and dipole moment surfaces of the active site model. The Conjugate gradient method is employed to optimize the cost functional and to obtain the optimized laser pulses. Optimized laser fields are found which give virtually 100% excitation probability to preselected vibrational levels. Similar application to hydrogen bonding in a complex system will also be presented.

Abstract

Abstract The trans Watson-Crick/Watson-Crick family of base pairs represent a geometric class which play important structural and possible functional roles in the ribosome, tRNA and other functional RNA molecules. They nucleate base triplets and quartets, participate as loop closing terminal base pairs in hair pin motifs and are also responsible for several tertiary interactions which enable sequentially distant regions to interact with each other in. Eleven representative examples spanning nine systems belonging to this geometric family of RNA base pairs, having widely different occurrence statistics in the PDB database, were studied at the HF/6-31G (d, p) level using Morokuma decomposition, Atoms in Molecule as well as Natural Bond Orbital methods in the optimized gas phase geometries and in their crystal structure geometries respectively. The BSSE and deformation energy corrected interaction energy values for the optimized geometries for non protonated base pairs ranged from -8.19 kcal/mol to -21.84 kcal/mol and compared favorably with those of canonical base pairs. The interaction energies of these base pairs, in their respective crystal geometries, were however lesser to varying extents and in one case, that of A:A W:W trans, it was actually found to be positive. The variation in RMSD between the two geometries was also large and ranged from 0.32 2.19 . Our analysis shows that the hydrogen bonding characteristics and interaction energies obtained, correlated with the nature and type of hydrogen bonds between base pairs; but the occurrence frequencies, interaction energies and geometric variabilities were conspicuous by the absence of any apparent correlation. Instead, the functional geometry of base pairs and the nature of their local interaction energy hyperspace, in conjunction with tertiary and neighboring group interaction potentials in the global context, could be correlated with the identities of free and bound hydrogen bond donor/acceptor groups present in interacting bases. It also suggests that the concept of isostericity alone may not always determine covariation potentials for base pairs, particularly those which may be participating in functional dynamics. These considerations are more important than the absolute values of the interaction energies in their respective optimized geometries in rationalizing their occurrences in functional RNAs. They highlight the importance of revising some of the existing DNA based structure analysis approaches and may have significant implications for RNA structure and dynamics, especially in the context of structure prediction algorithms.

Abstract

Abstract. The base pairing patterns in RNA structures are more versatile and completely different as compared to DNA. We present here results of ab-initio studies of structures and interaction energies of eight selected RNA base pairs reported in literature. Interaction energies, including BSSE correction, of hydrogen added crystal geometries of base pairs have been calculated at the HF/6-31G** level. The structures and interaction energies of the base pairs in the crystal geometry are compared with those obtained after optimization of the base pairs. We find that the base pairs become more planar on full optimization. No change in the hydrogen bonding pattern is seen. The dipole moments of the bases are reduced on full optimization. It is expected that the inclusion of appropriate considerations of many of these aspects of RNA base pairing would significantly improve the accuracy of RNA secondary structure prediction.

Abstract

Enthalpy entropy compensation effect has been a debatable topic for explaining the thermodynamic parameters in chemical reactions. Kinetic data for thermal degradation of chlorophylls (a, b and total) at 105145 C in coriander and mint leaf puree at pH 5.58.5 was used for this study. By applying the modified transition state theory and Krugs unbiased statistical regression procedure, the existence of thermodynamic compensation was tested for chlorophyll degradation. Enthalpy of activation (DH) for the coriander and mint purees ranged from 2.36 to 91.99 kJ/mol while entropy (DS) ranged from 0.047 to 0.713 kJ/(mol K). Though the enthalpy and entropy val- ues exhibited an excellent linear relationship (R2> 0.96), a critical analysis of the results indicated absence of any extra-thermodynamic effect or thermodynamic compensation for chlorophylls degradation. The presence of isokinetic point was also not detected.

Abstract

Optimal control theory is applied to obtain infrared laser pulses for selective vibrational excitation in a heteronuclear diatomic molecule. The problem of finding the optimized field is phrased as a maximization of a cost functional which depends on the laser field. A time dependent Gaussian factor is introduced in the field prior to evaluation of the cost functional for better field shape. Conjugate gradient method21,24 is used for optimization of constructed cost functional. At each instant of time, the optimal electric field is calculated and used for the subsequent quantum dynamics, within the dipole approximation. The results are obtained using both Morse potential as well as potential energy obtained using ab initio calculations.