Role of the Residue Q1919 in Increasing Kinase Activity of G2019S LRRK2 Kinase: A Computational Study

Mutations in multi-domain leucine-rich repeat kinase 2 (LRRK2) have been an interest to researchers as these mutations are associated with Parkinson's disease. G2019S mutation in LRRK2 kinase domain leads to the formation of additional hydrogen bonds by S2019 which results in stabilization of the active state of the kinase, thereby increasing kinase activity. Two additional hydrogen bonds of S2019 are reported separately. Here, a mechanistic picture of the formation of additional hydrogen bonds of S2019 with Q1919 (also with E1920) is presented using ‘active’ Roco4 kinase as a homology model and its relationship with the stabilization of the ‘active’ G2019S LRRK2 kinase. A conformational flipping of residue Q1919 was found which helped to form stable hydrogen bond with S2019 and made ‘active’ state more stable in G2019S LRRK2. Two different states were found within the ‘active’ kinase with respect to the conformational change (flipping) in Q1919. Two doubly-mutated systems, G2019S/Q1919A and G2019S/E1920 K, were studied separately to check the effect of Q1919 and E1920. For both cases, the stable S2 state was not formed, leading to a decrease in kinase activity. These results indicate that both the additional hydrogen bonds of S2019 (with Q1919 and E1920) are necessary to stabilize the active G2019S LRRK2.     

On the local fractional wave equation in fractal strings

The key aim of the present study is to attain nondifferentiable solutions of extended wave equation by making use of a local fractional derivative describing fractal strings by applying local fractional homotopy perturbation Laplace transform scheme. The convergence and uniqueness of the obtained solution by using suggested scheme is also examined. To determine the computational efficiency of offered scheme, some numerical examples are discussed. The results extracted with the aid of this technique verify that the suggested algorithm is suitable to execute, and numerical computational work is very interesting.     

Lattice vibronics of bcc phase metals (Ti,Zr and Hf) at higher temperatures

Ashcroft’s analytic bare ion pseudopotential form factor with a modified Hartree dielectric function has been employed to represent the temperature dependent interionic potential. This potential includes both direct ion-ion interaction and indirect ion-electron-ion interaction with and without the effects of ‘d’ bands, in some scantily studied complexbcc metals vizbcc Ti, Zr and Hf. The ab initio radial and tangential force constants extending out to 15th nearest neighbours are computed for the metals. The said potential is used for predicting the binding energy, elastic constants and phonon dispersion of the above mentioned metals and the results are satisfactorily compared with the corresponding measured data.     

Wind turbine noise measurement using a compact microphone array with advanced deconvolution algorithms

This paper experimentally investigates the noise from a large wind turbine (GE 1.5 MW) with a compact microphone array (OptiNav 24) using advanced deconvolution based beamforming methods, such as DAMAS and CLEAN-SC beamforming algorithms, for data reduction. Our study focuses on the ability of a compact microphone array to successfully locate both mechanical and aerodynamic noise sources on the wind turbine. Several interesting results have emerged from this study: (i) A compact microphone array is sufficient to perform a detailed study on wind turbine noise if advanced deconvolution methods are applied. (ii) Noise sources on the blade and on the nacelle can clearly be separated. (iii) Noise of the blades is dominated by trailing edge noise which is frequency dependent and is distributed along the length of the blade with the dominant noise source closer to the tip of the blade. (iv) The LP and DAMAS algorithms represent the distributed trailing edge noise source better than CLEAN-SC and classical beamforming. (v) Additional tonal noise produced during yawing operation is believed to be radiating from the tower of the wind turbine that acts like a resonator. (vi) Ground reflection is not believed to have a significant effect on noise source location estimates in this study.     

Meticulous assessment of natural compounds from NPASS database for identifying analogue of GRL0617, the only known inhibitor for SARS-CoV2 papain-like protease (PLpro) using rigorous computational workflow

Molecular Diversity - The latest global outbreak of 2019 respiratory coronavirus disease (COVID-19) is triggered by the inception of novel coronavirus SARS-CoV2. If recent events are of any...     

Identification of potential inhibitors of coronavirus hemagglutinin-esterase using molecular docking,molecular dynamics simulation and binding free energy calculation

Molecular Diversity - The pandemic outbreak of the Corona viral infection has become a critical global health issue. Biophysical and structural evidence shows that spike protein possesses a high...     

Flattened Gain Profile of Raman-Fiber Optical Parametric Hybrid Amplifier in C+L Band for SD-WDM System

Journal of Russian Laser Research - Variations in gain with the least noise figure and noise are the challenging issues for the hybrid amplifier. This is resolved in the proposed model of...     

Introduction to session 3

Applied Biochemistry and Biotechnology -     

Molecular simulation of the reversible mechanical unfolding of proteins

In this work we have combined a Wang-Landau sampling scheme [F. Wang and D. Landau, Phys. Rev. Lett. 86, 2050 (2001)] with an expanded ensemble formalism to yield a simple and powerful method for computing potentials of mean force. The new method is implemented to investigate the mechanical deformation of proteins. Comparisons are made with analytical results for simple model systems such as harmonic springs and Rouse chains. The method is then illustrated on a model 15-residue alanine molecule in an implicit solvent. Results for mechanical unfolding of this oligopeptide are compared to those of steered molecular dynamics calculations.