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

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 last two decades have seen increasing interest in the area of controlling dynamics at the atomic level. Among the several approaches used, Optimal Control Theory (OCT) has emerged as a powerful method for designing laser pulses to achieve 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 triatomics located in complex molecular environments. We use time dependent quantum mechanics to monitor the evolution of the system subject to a varying laser field. We have obtained fields for vibrational control of the diatomic system HF applying OCT using different algorithms, namely an iterative method, conjugate gradient method and genetic algorithms. The time-dependent quantum mechanical propagation of the system is achieved using the split operator form of the time evolution operator together with Fast Fourier transforms and grid methods. For the modelling of FeCO in carboxy-myoglobin, we use a two mathematical dimensional model. Density functional theory is used to obtain the potential energy and dipole moment surfaces of the active site model, while the conjugate gradient method is employed within the OCT optimization procedure to obtain the laser pulses. Optimized laser fields are found which give virtually 100% excitation probability to preselected vibrational levels. A similar application to a hydrogen bonded system of biological significance will also be presented. In all cases, detailed analyses of the field are carried out in terms of its power spectrum and the time variation of the contributions from the frequencies involved.

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

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

Predicting the 3D native conformation of a protein given the amino acid sequence is known as protein structure prediction (PSP)problem and is one of the greatest challenge of computational biology. The current work uses a real valued Genetic Algorithm (GA), a powerful variant of conventional GA to simulate the PSP problem. It consists of three evolutionary operators to manipulate the genes and a fitness function based on a simple force field. The individuals of the population correspond to different conformations of the same polypeptide chain, represented by a string of (phi,psi)torsion angles. The conformations are generated under the constraints of Ramachandran plot along with secondary structure information, which are then screened through a set of knowledge based biophysical filters, viz. persistence length and radius of gyration. Only the structures satisfying the filtering criteria are considered for energy minimization using GA. The algorithm has been validated on a set of known globular protein containing 2-4 secondary structure elements. For all the test proteins the algorithm converges rapidly ad the converged structure shows a backbone RMSD (root mean square deviation) or 3-6A as compared to the native structure.

Abstract

Controlling molecular energetics using laser pulses is exemplified for nuclear motion in two different diatomic systems. The problem of finding the optimized field for maximizing a desired quantum dynamical target is formulated using an iterative method. The method is applied for two diatomic sys- tems, HF and OH. The power spectra of the fields and evolution of populations of different vibrational states during transitions are obtained.

Abstract

Binding of Gold Nanoclusters with Size-Expanded DNA Bases: A Computational Study of Structural and Electronic Properties Purshotam Sharma, Himanshu Singh, Sitansh Sharma, and Harjinder Singh* Center for Computational Natural Sciences and Bioinformatics, International Institute of Information and Technology, Gachibowli, Hyderabad-500032, India Received June 15, 2007 Abstract: Binding of gold nanoclusters with size-expanded DNA bases, xA, xC, xG, and xT, is studied using quantum chemical methods. Geometries of the neutral xA-Au6, xC-Au6, xG-Au6, and xT-Au6 complexes were fully optimized using the B3LYP density functional method (DFT). 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 aromatic character 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

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.

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.