Abstract

t has been proposed that combining chemical and thermal denaturation along with mechanical unfolding enables better understanding of the thermodynamics of protein folding, and associated pathways. We have used molecular dynamics (MD) simulations, and umbrella sampling technique to study the effect of thermal and chemical perturbations on the unfolding of Trp-cage miniprotein (TC5b). Free energy profiles for the unfolding of the minicage protein were obtained at two different temperatures, and in presence and absence of urea. The distance between the penultimate terminal residues was used as the reaction coordinate for calculating the free energies. The unfolding involves opening of the Trp-cage, and separation of the secondary structure elements followed by the unfolding of the α-helix. Several energetic and geometric analyses including inter- and intramolecular interactions, and radial distribution functions and their relevance to the folding pathways will be discussed. Similar study on the titin I27 protein will also be presented.

Abstract

SAM-III riboswitch present in the 5’-UTR of mRNA that translates to SAM synthetase in certain bacteria is involved in regulating the biosynthesis of S-adenosylmethionine (SAM) by acting as an on-off switch for the translation process. We have used molecular dynamics (MD) and steered MD simulations to understand the ligand recognition and the switching mechanisms. Computations on model systems indicated that the riboswitch does not recognize SAM over a structurally related analog, S-adenosylhomocysteine (SAH). Nonetheless, the RNA uses nonspecific interactions to stabilize SAM in its binding pocket compared to SAH. Calculations were done in the absence of the ligand to examine the conformational changes responsible for the transition between on and off states. While the on- state is capable of sampling a large conformational space, formation of duplexlike structure comprising the adenine part of the ligand and sequentially distant nucleotides seems to be crucial for the on- to off- state transition.

Abstract

Vpu is an 81-residue protein encoded by human immunodeficiency virus type I (HIV-1) that facilitates viral release from host cells. The protein has a cytoplasmic domain and a helical transmembrane (TM) domain, of which the latter oligomerizes to form cation-specific ion channels. The number of TM domains that constitute the channel is still unclear, with experimental studies indicating the existence of a variety of oligomeric states. In this study, we have examined the possibility of Vpu to exist in tetra-, penta-, and hexameric states using comprehensive molecular dynamics (MD) simulations. By modeling the TM domain as an ideal α-helix, we carried out replica-exchange MD simulations in an implicit membrane environment for obtaining suitable starting structures, which were then subjected to extensive MD simulations in a fully hydrated lipid bilayer environment. The results show that the pentameric form is the most stable oligomeric state (the tetramer and hexamer models lose their initial channel-like structure), with helices in the pentamer being held together by strong van der Waals interactions. Hydrogen bonds between lipid headgroups and basic/hydrophilic residues on the protein are stronger in the pentamer than in the tetramer or the hexamer, indicating that these interactions might play a role in adhering the pentamer to the membrane. Free energy calculations using umbrella sampling technique have been performed to examine the potassium ion permeation through the pentameric pore. The results show a high free energy barrier corresponding to ion transport indicating weak ion channel activity in agreement with previous experimental biophysical studies.

Abstract

Chemical modifications on the backbone of the oligonucleotides have been shown to improve several factors such as increased cellular uptake, altered duplex conformation and stability. Modified oligonucleotides have also been shown to be potential antisense agents. Some of the common modifications include 2'-O-methyl, 2'-O,4'-C-methylene--D-ribofuranosyl (LNA) and phosphoroamidate. In general, the modifications at ribose sugar of the oligonucleotide attribute special features to the duplexes than other modifications. Molecular dynamics (MD) simulations are valuable tools to study their dynamics, conformational preferences, stabilities etc. Here, we have employed different simulation techniques such as classical MD, replica exchange MD to understand the impact of modification on the duplex properties. The simulations revealed several important aspects related to duplex stability and relation with their base content. Our results also suggest that the differential changes observed in nucleic acids depends on the position, nature of the modified site. This study also provides a molecular level picture for the origin of structural changes arise due to different types of modifications which is very important in designing the most fruitful antisense oligonucleotides.

Abstract

Pipeline generally extends over long distances traversing through wide variety of different soils, geological conditions and regions with different seismicity. Majority of the past works in the area of pipeline subjected to fault motion is restricted in several ways. There were many analytical models developed in the past for pipeline fault crossing, however, they are of limited usage, for example analytical model developed for pipeline fault crossing can be useful for strike slip fault crossing only. Likewise incorporating the large geometric changes in analytical study is a tricky task; however pipeline subjected to the fault motion itself is a phenomenon of large geometric changes. Especially when pipeline subjected to compression, where in addition to material deformation it also undergoes general as well as local buckling with bending, contradictorily past work mostly assumed that pipeline is under tension. With day by day increasing capacity of computation and advancement in numerical modeling, one can find more facts for pipeline subjected fault motions including cases of pipe under compression as well. In this paper, past work is reviewed for pipeline subjected to large fault motion. A three dimensional FE based numerical model is suggested to carry out pipeline performance of buried pipeline subjected to fault motion. A proposed model includes material nonlinearity, as well as effect of the large geometric changes. For this purpose, three dimensional FE program is developed in MATLAB. Displacement controlled Arc-length technique is implemented to solve the nonlinear behavior. To reduce the computation time of analysis here parallelization tool kit of MATLAB is utilized.

Abstract

Pounding between adjacent structures is commonly observed phenomenon during earthquakes. In metropolitan areas, due to increasing population and land values buildings have been constructed very close to each other. Although seismic pounding between adjacent structures is considered in codal provisions, the practice of construction is still a problem in developing countries resulting more vulnerable during earthquakes. To study the effect of structural pounding, a case study has been done on different setbacks and storey heights of two adjacent structures using SAP 2000. The pounding responses of two structures and collision forces are calculated. The effect of collision is more when structures are kept at extreme levels of setback. When the structures are kept at different elevation levels (setback=0), the pounding response changes significantly as the height of structure decreases.

Abstract

Abstract: Pounding between adjacent structures is commonly observed phenomenon during major earthquakes which may cause both architectural and structural damages. Generally most of the existing buildings in seismically moderate regions are built without codal provisions. In the event of earthquake, pounding may cause considerable damage and leads to collapse of the colliding structures if the separation distance is insufficient. The aim of this paper is to study the impact of first collision according to the codal provisions for five different earthquakes. For this purpose we considered two buildings and the same were idealized as linear single degree of freedom oscillators. Separation distance between buildings is provided accoding to codal provisions of various countries and the buildings are subjected to different ground motions of PGA ranging from 0.22 g to 0.88 g. Later impact force due to collision is calculation and the results were analyzed.

Abstract

It is not uncommon to find buildings in seismically active regions built adjacent to each other without following the prescribed codal separation distance. If the separation distance is insufficient, in the event of an earthquake, pounding may cause severe architectural and structural damage, and may even lead to the collapse of the structure. Seismic design codes suggest minimum separation distance between two adjacent structures; however, the spacing has to be enough to withstand earthquake excitations. To understand the effect of codal provisions on pounding, two buildings were idealised as linear single degree of freedom oscillators. The separation distance between them was provided following the codal provisions of select countries. By subjecting the buildings to five different ground motions the first impact force due to collision was calculated and the results were analysed to compare the codal provisions.

Abstract

Reinforced concrete buildings constitute the dominant type of construction in the earthquake prone countries. Many researchers have studied the performance of the RC structure in seismic environment. In this study a RC building of four storeys is considered and its performance is evaluated when subjected to five ground motions. The study is roughly divided into three parts, first part includes investigation of the dynamic characteristics of ground excitations, second part includes evaluation of the nonlinear seismic behaviour of building subjected to the given ground excitations and third part includes evaluation of damage. The present study is based on analytical investigation of seismic performance and potential seismic damage of a reinforced concrete framed building due to earthquakes in India, using nonlinear modelling and displacement-based analysis techniques. Since the seismic damage is directly correlated to the displacement (deformation) of the structure, the yield displacement of the structure is evaluated from the pushover analysis. From the displacement time history of the structure response, the peak values which exceeding yield displacement of the structure have been identified and the hysteresis energy is calculated for each cycle to calculate the damage of the structure. The estimation of structural damage is calculated as per the model of Park and Ang. At the end, authors attempted to propose a new damage scale.

Abstract

Brick masonry type of construction is found all over India and neighbouring countries like Nepal and Bangladesh. In India, these buildings are commonly found in North, extending from Punjab to West Bengal and Central India, from Haryana to Madhya Pradesh. These buildings are most commonly found in regions where good quality clay for brick production is abundantly available (World housing encyclopaedia report, 2003). But, past earthquakes witness major loss to brick masonry type of buildings. Many analytical and experimental studies have been done in past to understand the behaviour of brick masonry buildings during earthquake. Analytical study mainly includes, numerical modelling of the brick masonry buildings of type URM and Reinforced concrete Infill wall. In this work, primary focus is given to numerical modelling and nonlinear behaviour of brick masonry buildings subjected to lateral loads and understanding crack propagation in wall and calculation of quantitative damage to the building in terms of stiffness, ductility in load displacement curve.