Browsing by Subject "Molecular dynamics simulations"

Now showing 1 - 7 of 7

Open Access
A small non-interface surface epitope in human IL18 mediates the dynamics and self-assembly of IL18-IL18BP heterodimers
(Elsevier, 2023-07-01) Yazıcı, Yılmaz Yücehan; Belkaya, Serkan; Timuçin, E.
Interleukin 18 (IL18) is a pro-inflammatory cytokine that modulates innate and adaptive immune responses. IL18 activity is tightly controlled by the constitutively secreted IL18 binding protein (IL18BP). PDB structures of human IL18 showed that a short stretch of amino acids between 68 and 81 adopted a disordered conformation in all IL18-IL18BP complexes while adopting a 310 helical structure in other IL18 structures, including the receptor complexes. The C74 of human IL18, which was reported to form a novel intermolecular disulfide bond in the human tetrameric assembly, is also located in this short epitope. These observations reflected the importance of this short surface epitope for the structure and dynamics of the IL18-IL18BP heterodimers. We have analyzed all known IL18-IL18BP complexes in the PDB by all-atom MD simulations. The analysis also included two computed complex models adopting a helical structure for the surface epitope. Heterodimer simulations showed a stabilizing impact of the small surface region at the helical form by reducing flexibility of the complex backbone. Analysis of the symmetry-related human IL18-IL18BP tetramer showed that the unfolding of this small surface region also contributed to the IL18-IL18BP stability through a completely exposed C74 sidechain to form an intermolecular disulfide bond in the self-assembled human IL18-IL18BP dimer. Our findings showed how the conformation of the short IL18 epitope between amino acids 68 and 81 would affect IL18 activity by mediating the intermolecular interactions of IL18.
Open Access
Atomic, electronic, and transport properties of quantum point contacts on graphite surface
(1997) Kılıç, Çetin
In this thesis, the variation of conductance through a contact formed by a hard STM tip pressing on a graphite substrate is investigated. Our study involves the molecular dynamics simulations to reveal the evolution of the atomic structure during the growth of the contact, and ab initio electronic structure calculations of graphite that is under expansive and compressive strain along the [0001] axis. Combining the results obtained from these calculations, we propose a mechanism to explain the peculiar variation of the conductance. Owing to the layered structure of graphite, the variation of conductance exhibits dramatic differences from that of normal metals. It is predicted that in graphite, the conductance first increases, and then drops to a lower value with the puncture of the atomic plane. This phenomenon repeats quasi-periodically as the tip continues to press on the surface.
Open Access
Conductance through atomic contacts created by scanning tunneling microscopy
(Elsevier, 1999) Kiliç, Ç.; Mehrez, H.; Çıracı, Salim; Batra, I. P.
We investigate conductance through contacts created by pressing a hard tip, as used in scanning tunneling microscopy, against substrates. Two different substrates are considered, one a normal metal (Cu) and another a semi-metal (graphite). Our study involves the molecular dynamics simulations for the atomic structure during the growth of the contact, and selfconsistent field electronic structure calculations of deformed bodies. We develop a theory predicting the conductance variations as the tip approaches the surface. We offer an explanation for a quasiperiodic variation of conductance of the contact on the graphite surface, a behavior which is dramatically different from contacts on normal metals.
Open Access
Hierarchical self-assembly of histidine-functionalized peptide amphiphiles into supramolecular chiral nanostructures
(American Chemical Society, 2017) Koc, M. H.; Ciftci, G. C.; Baday, S.; Castelletto, V.; Hamley, I. W.; Güler, Mustafa O.
Controlling the hierarchical organization of self-assembling peptide amphiphiles into supramolecular nanostructures opens up the possibility of developing biocompatible functional supramolecular materials for various applications. In this study, we show that the hierarchical self-assembly of histidine- (His-) functionalized PAs containing d- or l-amino acids can be controlled by both solution pH and molecular chirality of the building blocks. An increase in solution pH resulted in the structural transition of the His-functionalized chiral PA assemblies from nanosheets to completely closed nanotubes through an enhanced hydrogen-bonding capacity and π-π stacking of imidazole ring. The effects of the stereochemistry and amino acid sequence of the PA backbone on the supramolecular organization were also analyzed by CD, TEM, SAXS, and molecular dynamics simulations. In addition, an investigation of chiral mixtures revealed the differences between the hydrogen-bonding capacities and noncovalent interactions of PAs with d- and l-amino acids.
Open Access
Hypergraph models for parallel sparse matrix-matrix multiplication
(2015-09) Akbudak, Kadir
Multiplication of two sparse matrices (i.e., sparse matrix-matrix multiplication, which is abbreviated as SpGEMM) is a widely used kernel in many applications such as molecular dynamics simulations, graph operations, and linear programming. We identify parallel formulations of SpGEMM operation in the form of C = AB for distributed-memory architectures. Using these formulations, we propose parallel SpGEMM algorithms that have the multiplication and communication phases: The multiplication phase consists of local SpGEMM computations without any communication and the communication phase consists of transferring required input/output matrices. For these algorithms, three hypergraph models are proposed. These models are used to partition input and output matrices simultaneously. The input matrices A and B are partitioned in one dimension in all of these hypergraph models. The output matrix C is partitioned in two dimensions, which is nonzero-based in the rst hypergraph model, and it is partitioned in one dimension in the second and third models. In partitioning of these hypergraph models, the constraint on vertex weights corresponds to computational load balancing among processors for the multiplication phase of the proposed SpGEMM algorithms, and the objective, which is minimizing cutsize de ned in terms of costs of the cut hyperedges, corresponds to minimizing the communication volume due to transferring required matrix entries in the communication phase of the SpGEMM algorithms. We also propose models for reducing the total number of messages while maintaining balance on communication volumes handled by processors during the communication phase of the SpGEMM algorithms. An SpGEMM library for distributed memory architectures is developed in order to verify the empirical validity of our models. The library uses MPI (Message Passing Interface) for performing communication in the parallel setting. The developed SpGEMM library is run on SpGEMM instances from various realistic applications and the experiments are carried out on a large parallel IBM BlueGene/Q system, named JUQUEEN. In the experimentation of the proposed hypergraph models, high speedup values are observed.
Open Access
Molecular investigation of polyelectrolyte hydrogel under mechanical deformation
(2023-07) Rafique, Muzaffar
Polyelectrolyte hydrogels are fascinating materials that can produce electromechanical responses when they are electrically or mechanically deformed. However, the accurate molecular origins of such phenomenon are still unknown, even though it is often ascribed to the change in condensation of counterion levels or alteration of ionic conditions in the pervaded volume of the hydrogel. We used all-atom molecular dynamics (MD) simulations to investigate this behavior by utilizing a polyacrylic acid (PAA) hydrogel immersed in an explicit polar solvent as our model system. In the atomistic MD simulation, we investigated the swelling behavior of polyelectrolyte hydrogels, traditionally computed through the equilibrium of chemical potential and pressure between the system and reservoir. However, we discovered that achieving the equilibrium swelling state was non-trivial, as faster relaxation of the simulation box resulted in lower swelling ratios, while slower relaxation led to larger swelling ratios. To address this challenge, we employed theoretical calculations with a Gaussian state as the reference to estimate the hydrogel’s swelling ratio effectively. In our computational study, we investigated the response of PAA polyelectrolyte hydrogel from weak to highly swollen (i.e., between 60 to 90% solvent content) when subjected to uniaxial mechanical compression and extension. Our primary aim is to compute the condensed counterions at different deformations at the microscopic level. We found out that condensation of counterion shows highly non-monotonic behavior when they are mechanically deformed, with an overall increase in total counterion condensation when the PAA hydrogel is uniaxially compressed or stretched. However, this effect diminishes for weakly swollen gel because a large fraction of counterions are already condensed on the polyelectrolyte polymer. Upon closer examination, we found that counterion condensation increases along the stretched chains in the hydrogel. on the one hand, this increase reaches to maximum value for certain deformation ratios after that, we see a decline in the condensation of counterions when the hydrogel chains are stretched further. On the other hand, we see a very minimal increase in condensation when the hydrogel is compressed, and chains are collapsed state. We also analyzed the single polyelectrolyte chains, which also displayed a qualitatively similar response. This observation gives us insight that polymer chain conformations affect the distribution of counterions in the gel. We further investigated the counterion condensation behavior for polyelectrolyte solutions at their critical concentration level. However, we don’t see any deformation-dependent counterion condensation. This suggests the importance of hydrogel topology, which constrains the polyelectrolyte chain ends and leads to the observed behavior. These extensive molecular dynamics simulations shed light on the interesting and heterogeneous behavior of counterion condensation when the hydrogel is deformed, showing a rich electrostatic response behavior. These findings contribute significantly to the understanding of the underlying behavior of mechanically deformed polyelectrolyte hydrogels.
Open Access
Protein-DNA dissociation kinetics and chromosome organization in a model bacterial confinement
(2021-09) Koşar, Zafer
Transcriptional initiation and repression require the temporal interactions of transcription factors with DNA. Recent experiments showed that the interaction lifetime is crucial for transcriptional regulation. Relevantly, in vitro single-molecule studies showed that nucleoid-associated proteins (NAPs) dissociate rapidly from DNA through facilitated dissociation (FD) with the increasing phase-solution protein concentration. Nevertheless, it is not clear whether such a concentration-dependent mechanism is functional in bacterial confinement, in which NAP levels and the 3D chromosomal architecture are coupled. Here, we employ extensive coarse-grained molecular simulations, where we model the dissociation of specific and nonspecific dimeric NAPs from a high-molecular-weight circular DNA polymer in a rod-shaped structure constituting the cellular boundaries. Our simulations indicate that the peak cellular protein concentrations result in highly compact chromosomal conformations. Such compactions lead to shorter DNA-residence times but only for NAPs demonstrating sequence-specificity, such as the factor for inversion stimulation (Fis). On the other hand, the dissociation rates of nonspecific NAPs decrease with the increasing protein concentrations, exhibiting an inverse FD behavior. Another set of simulations utilizing restrained chromosome models reveal DNA-segmental fluctuations as the cause of this reversed response, suggesting that moderate chromosomal compaction promotes protein dissociation. Together, our findings suggest that cellular quantities of structural DNA-binding proteins could be highly influential on their residence times and the chromosome architecture.