Density functional theory analysis and spectral studies on amyloid peptide Aβ(28–35) and its mutants A30G and A30I

Nagarajan, Sureshbabu; Rajadas, Jayakumar; Malar, E. J. Padma

doi:10.1016/j.jsb.2010.02.017

Cited by 5 publications

(3 citation statements)

References 50 publications

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“…The coil conformer of the tetrapeptide can retain the two NH···OC bonds that are present in the coil cluster. It is well-known that NH···OC HBs between amino acid residues play a central role in stabilizing the α-helical, 3 10 helical, and random coil secondary structures in peptides. , As the size of the cluster increases, the number of NH···OC bonds in the coil arrangement will increase. This would lead to the dominance of the coil cluster as it would possess lower energy than the linear or cyclic clusters.…”

Section: Results and Discussionmentioning

confidence: 99%

Structural Stability in Dimer and Tetramer Clusters of l-Alanine in the Gas Phase and the Feasibility of Peptide Bond Formation

Malar

Divya

2018

J. Phys. Chem. B

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Stability in low-energy structures of the dimer and tetramer clusters of l-alanine in the gas phase is studied by accurate quantum chemical computations at the DLPNO2013-CCSD(T) level. It is found that the dispersion interaction energies in the dimer (-0.3 to -0.6 kcal/mol) and in the tetramer (-1.3 to -2.5 kcal/mol) have a small role in the stability of the clusters as compared to the hydrogen bond (HB) energies -4.1 to -14.2 and -32.2 to -40.1 kcal/mol, respectively. The HB energy in the alanine cluster is obtained from the binding energy (BE) of DLPNO2013-CCSD(T)//B2PLYP/def2-TZVP by subtracting the dispersion interaction energy. Local HB energies deduced from the dimer structures are found to be suitable to estimate total HB energies in similar environments. The BEs of OH···NH and OH···OC bonds are -9.5 and -7.1 kcal/mol, respectively. This suggests that the higher clusters are formed through OH···NH bonds as they confer more stability. Analysis of bonding in the tetramer shows that the low-energy tetramer and higher clusters are formed through the OH···NH mode of hydrogen bonding, unlike the dimer which is formed through the OH···OC bond. Feasibility of the amino acid cluster to function as a precursor for polypeptide formation is examined because the orientation of the OH···NH mode of hydrogen bonding is suitable for chemical condensation. The propensity of forming coiled structures in higher clusters and thus in the polypeptides is examined based on the conformational stability in the tetramer of alanine.

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Section: Results and Discussionmentioning

confidence: 99%

Structural Stability in Dimer and Tetramer Clusters of l-Alanine in the Gas Phase and the Feasibility of Peptide Bond Formation

Malar

Divya

2018

J. Phys. Chem. B

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“…System 1 is a copper complex with four ligands having 158 electrons and described with a cc-pVDZ basis set. System 2 is a polypeptide taken from reference [24] (434 electrons and 6-31G * basis set). System 3 is identical to System 2 but using a larger basis set, namely the cc-pVTZ basis set.…”

Section: The Degree Of Localization Of the Standard Atomicmentioning

confidence: 99%

Quantum Monte Carlo for large chemical systems: Implementing efficient strategies for petascale platforms and beyond

et al. 2013

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Various strategies to implement efficiently quantum Monte Carlo (QMC) simulations for large chemical systems are presented. These include: (i) the introduction of an efficient algorithm to calculate the computationally expensive Slater matrices. This novel scheme is based on the use of the highly localized character of atomic Gaussian basis functions (not the molecular orbitals as usually done), (ii) the possibility of keeping the memory footprint minimal, (iii) the important enhancement of single-core performance when efficient optimization tools are used, and (iv) the definition of a universal, dynamic, fault-tolerant, and load-balanced framework adapted to all kinds of computational platforms (massively parallel machines, clusters, or distributed grids). These strategies have been implemented in the QMC=Chem code developed at Toulouse and illustrated with numerical applications on small peptides of increasing sizes (158, 434, 1056, and 1731 electrons). Using 10-80 k computing cores of the Curie machine (GENCI-TGCC-CEA, France), QMC=Chem has been shown to be capable of running at the petascale level, thus demonstrating that for this machine a large part of the peak performance can be achieved. Implementation of large-scale QMC simulations for future exascale platforms with a comparable level of efficiency is expected to be feasible.

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“…Molecular dynamics simulation techniques can be applied to study the behavior of both intact and mutated GK structures at any specified conditions, which can be used to investigate its specific molecular interaction in the system [14–16]. The dynamic simulations can explain the interaction and charge distribution of GK using density functional theory calculations in both intact and mutated structures [17]. This technique can also explain the impact of environmental conditions such as solvation and temperature on the GK conformations and energy changes which are of fundamental importance to describe the function and activity.…”

Section: Introductionmentioning

confidence: 99%

Structural Variations of Human Glucokinase Glu256Lys in MODY2 Condition Using Molecular Dynamics Study

Yellapu

Kandlapalli

Valasani

et al. 2013

Biotechnology Research International

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Glucokinase (GK) is the predominant hexokinase that acts as glucose sensor and catalyses the formation of Glucose-6-phosphate. The mutations in GK gene influence the affinity for glucose and lead to altered glucose levels in blood causing maturity onset diabetes of the young type 2 (MODY2) condition, which is one of the prominent reasons of type 2 diabetic condition. In view of the importance of mutated GK resulting in hyperglycemic condition, in the present study, molecular dynamics simulations were carried out in intact and 256 E-K mutated GK structures and their energy values and conformational variations were correlated. Energy variations were observed in mutated GK (3500 Kcal/mol) structure with respect to intact GK (5000 Kcal/mol), and it showed increased γ-turns, decreased β-turns, and more helix-helix interactions that affected substrate binding region where its volume increased from 1089.152 Å2 to 1246.353 Å2. Molecular docking study revealed variation in docking scores (intact = −12.199 and mutated = −8.383) and binding mode of glucose in the active site of mutated GK where the involvement of A53, S54, K56, K256, D262 and Q286 has resulted in poor glucose binding which probably explains the loss of catalytic activity and the consequent prevailing of high glucose levels in MODY2 condition.

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Density functional theory analysis and spectral studies on amyloid peptide Aβ(28–35) and its mutants A30G and A30I

Cited by 5 publications

References 50 publications

Structural Stability in Dimer and Tetramer Clusters of l-Alanine in the Gas Phase and the Feasibility of Peptide Bond Formation

Structural Stability in Dimer and Tetramer Clusters of l-Alanine in the Gas Phase and the Feasibility of Peptide Bond Formation

Quantum Monte Carlo for large chemical systems: Implementing efficient strategies for petascale platforms and beyond

Structural Variations of Human Glucokinase Glu256Lys in MODY2 Condition Using Molecular Dynamics Study

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