Energy, mobility, and structural profiles of residues in a specific sequence of human immunodefic... more Energy, mobility, and structural profiles of residues in a specific sequence of human immunodeficiency virus (HIV)-1 protease chain and its global conformation and dynamics are studied by a coarse-grained computer simulation model on a cubic lattice. HIV-1 protease is described by a chain of 99 residues (nodes) in a specific sequence (1DIFA) with N- and C-terminals on the lattice, where empty lattice sites represent an effective solvent medium. Internal structures of the residues are ignored but their specificities are captured via an interaction (εij) matrix (residue-residue, residue-solvent) of the coefficient (fεij) of the Lennard-Jones potential. Simulations are performed for a range of interaction strength (f) with the solvent-residue interaction describing the quality of the solvent. Snapshots of the protein show considerable changes in the conformation of the protein on varying the interaction. From the mobility and energy profiles of the residues, it is possible to identify the active (and not so active) segments of the protein and consequently their role in proteolysis. Contrary to interaction thermodynamics, the hydrophobic residues possess higher configurational energy and lower mobility while the electrostatic and polar residues are more mobile despite their lower interaction energy. Segments of hydrophobic core residues, crucial for the structural evolution of the protein are identified—some of which are consistent with recent molecular dynamics simulation in context to possible clinical observations. Global energy and radius of gyration of the protein exhibit nonmonotonic dependence on the interaction strength (f) with opposite trends, e.g., rapid transition into globular structure with higher energy. Variations of the rms displacement of the protein and that of a tracer residue, Gly49, with the time steps show how they slow down on increasing the interaction strength.
A stochastic cellular automata (SCA) approach is introduced to study the growth and decay of cell... more A stochastic cellular automata (SCA) approach is introduced to study the growth and decay of cellular population in an immune response model relevant to HIV. Four cell types are considered: macrophages (M), helper cells (H), cytotoxic cells (C), and viral infected cells (V). Mobility of the cells is introduced and viral mutation is considered probabilistically. In absence of mutation, the
The nitroxide spin label is the most widely used probe for electron paramagnetic resonance (EPR) ... more The nitroxide spin label is the most widely used probe for electron paramagnetic resonance (EPR) spectroscopy studies of the structure and function of biomolecules. However, the role of surrounding environments in determining the dynamics of nitroxide spin labels in biological complex systems remains to be clarified. This study aims to characterize the dynamics and environmental structure of spin labels in the voltage-sensing domain (VSD) of a KvAP potassium channel by means of molecular dynamics (MD) studies. MD simulations for unlabeled and 132 spin-labeled KvAP-VSD models (spin labels introduced at positions 20-151) were carried out in a phospholipid bilayer to evaluate conformational dynamics of nitroxide spin-label side chains in the VSD. Structural flexibility, conformational freedom, and orientation of the spin-label side chains were investigated in relation to their dynamics in different microenvironments. The analysis of MD data showed that the attached spin-label probe did not severely perturb the protein dynamics. The conformational freedoms of the nitroxide side chain vary with the physical structure of the surrounding environments. The two terminal dihedral angles of the nitroxide side chain tend to cluster and adopt several preferred rotameric states. From the nearest-neighbor analysis, the spin label can be exposed to either a homogeneous or heterogeneous environment with various exposure scenarios. The dynamical movement of KvAP-VSD is high at a water-exposed site, moderate in the membrane, and low in the protein core. Understanding the structure and dynamics behaviors of spin labels helps to manage the experimental uncertainty and avoid misleading interpretation in relation to the protein structure.
Abstract A discrete lattice of size L x× L y× L z is considered with a large aspect ratio L_x/L_y... more Abstract A discrete lattice of size L x× L y× L z is considered with a large aspect ratio L_x/L_y (L_z). Polymer chains, each of length L c are released from one end (x= 0) of the sample in presence of a field (E) along x-direction. In addition to excluded volume, a nearest neighbor repulsive interaction is considered among the polymer nodes. Metropolis algorithm is used to move chain nodes: kink-jump dynamics is primarily used in this study, however, attempts are made to explore the effects of other dynamics such as crank-shaft and reptation. As ...
A Monte Carlo simulation is performed to study the evolution of the density profile of the chains... more A Monte Carlo simulation is performed to study the evolution of the density profile of the chains and their size near an adsorbing wall. We consider a two dimensional lattice of size Lx × L_y. Polymer chains are positively charged and released from one end of the sample (the source end) at a constant rate. A nearest neighbor polymer-polymer repulsive interaction is considered and an external field is applied to drive the chains along the X-direction where a wall is placed opposite to the source end. We consider attractive, neutral, and repulsive interactions beween the wall and the chain nodes. Metropolis algorithm is used to reptate the chains. We investigate the evolution of the density profile of the chains as they deposit on the wall as a function of chain length, field strength, and temperature. The profile of the size of the chains is also examined by studying the evolution of the radius of gyration (R_g) and end-to-end distance (R_e) of the chains. We observe several interesting results such as the onset of oscillation in density profile, variation of the polymer coverage on the wall with chain length, field, temperature, etc.
Energy, mobility, and structural profiles of residues in a specific sequence of human immunodefic... more Energy, mobility, and structural profiles of residues in a specific sequence of human immunodeficiency virus (HIV)-1 protease chain and its global conformation and dynamics are studied by a coarse-grained computer simulation model on a cubic lattice. HIV-1 protease is described by a chain of 99 residues (nodes) in a specific sequence (1DIFA) with N- and C-terminals on the lattice, where empty lattice sites represent an effective solvent medium. Internal structures of the residues are ignored but their specificities are captured via an interaction (εij) matrix (residue-residue, residue-solvent) of the coefficient (fεij) of the Lennard-Jones potential. Simulations are performed for a range of interaction strength (f) with the solvent-residue interaction describing the quality of the solvent. Snapshots of the protein show considerable changes in the conformation of the protein on varying the interaction. From the mobility and energy profiles of the residues, it is possible to identify the active (and not so active) segments of the protein and consequently their role in proteolysis. Contrary to interaction thermodynamics, the hydrophobic residues possess higher configurational energy and lower mobility while the electrostatic and polar residues are more mobile despite their lower interaction energy. Segments of hydrophobic core residues, crucial for the structural evolution of the protein are identified—some of which are consistent with recent molecular dynamics simulation in context to possible clinical observations. Global energy and radius of gyration of the protein exhibit nonmonotonic dependence on the interaction strength (f) with opposite trends, e.g., rapid transition into globular structure with higher energy. Variations of the rms displacement of the protein and that of a tracer residue, Gly49, with the time steps show how they slow down on increasing the interaction strength.
A stochastic cellular automata (SCA) approach is introduced to study the growth and decay of cell... more A stochastic cellular automata (SCA) approach is introduced to study the growth and decay of cellular population in an immune response model relevant to HIV. Four cell types are considered: macrophages (M), helper cells (H), cytotoxic cells (C), and viral infected cells (V). Mobility of the cells is introduced and viral mutation is considered probabilistically. In absence of mutation, the
The nitroxide spin label is the most widely used probe for electron paramagnetic resonance (EPR) ... more The nitroxide spin label is the most widely used probe for electron paramagnetic resonance (EPR) spectroscopy studies of the structure and function of biomolecules. However, the role of surrounding environments in determining the dynamics of nitroxide spin labels in biological complex systems remains to be clarified. This study aims to characterize the dynamics and environmental structure of spin labels in the voltage-sensing domain (VSD) of a KvAP potassium channel by means of molecular dynamics (MD) studies. MD simulations for unlabeled and 132 spin-labeled KvAP-VSD models (spin labels introduced at positions 20-151) were carried out in a phospholipid bilayer to evaluate conformational dynamics of nitroxide spin-label side chains in the VSD. Structural flexibility, conformational freedom, and orientation of the spin-label side chains were investigated in relation to their dynamics in different microenvironments. The analysis of MD data showed that the attached spin-label probe did not severely perturb the protein dynamics. The conformational freedoms of the nitroxide side chain vary with the physical structure of the surrounding environments. The two terminal dihedral angles of the nitroxide side chain tend to cluster and adopt several preferred rotameric states. From the nearest-neighbor analysis, the spin label can be exposed to either a homogeneous or heterogeneous environment with various exposure scenarios. The dynamical movement of KvAP-VSD is high at a water-exposed site, moderate in the membrane, and low in the protein core. Understanding the structure and dynamics behaviors of spin labels helps to manage the experimental uncertainty and avoid misleading interpretation in relation to the protein structure.
Abstract A discrete lattice of size L x× L y× L z is considered with a large aspect ratio L_x/L_y... more Abstract A discrete lattice of size L x× L y× L z is considered with a large aspect ratio L_x/L_y (L_z). Polymer chains, each of length L c are released from one end (x= 0) of the sample in presence of a field (E) along x-direction. In addition to excluded volume, a nearest neighbor repulsive interaction is considered among the polymer nodes. Metropolis algorithm is used to move chain nodes: kink-jump dynamics is primarily used in this study, however, attempts are made to explore the effects of other dynamics such as crank-shaft and reptation. As ...
A Monte Carlo simulation is performed to study the evolution of the density profile of the chains... more A Monte Carlo simulation is performed to study the evolution of the density profile of the chains and their size near an adsorbing wall. We consider a two dimensional lattice of size Lx × L_y. Polymer chains are positively charged and released from one end of the sample (the source end) at a constant rate. A nearest neighbor polymer-polymer repulsive interaction is considered and an external field is applied to drive the chains along the X-direction where a wall is placed opposite to the source end. We consider attractive, neutral, and repulsive interactions beween the wall and the chain nodes. Metropolis algorithm is used to reptate the chains. We investigate the evolution of the density profile of the chains as they deposit on the wall as a function of chain length, field strength, and temperature. The profile of the size of the chains is also examined by studying the evolution of the radius of gyration (R_g) and end-to-end distance (R_e) of the chains. We observe several interesting results such as the onset of oscillation in density profile, variation of the polymer coverage on the wall with chain length, field, temperature, etc.
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Papers by Ras Pandey