Molecular Modeling of Biological Systems: from a Force Field Study to Modeling of an Anti-Microbial Peptide in Water and a Complex S. aureus Membrane

Interest in studying anti-microbial peptides (AMPs) has increased because of their potential as a future applicable antibiotic drug. In my research under supervision of Professor Greenfield, we attempt to understand the interaction of AMPs against membrane of bacteria. We are studying the structure of two novel hybrid AMPs LM7-1 and LM7-2 that were designed previously in Professor Martin’s research group (Cell and Molecular Biology Department). These AMPs differ in sequence only at the 15th residue. Several experimental studies have been successfully investigated mechanisms of AMPs against bacteria, but there is still much uncertainty in the exact mechanisms because of experimental restrictions. Since molecular modeling provides atomistic details and 3D structure of a system, it can significantly contribute to investigating these mechanisms in more detail. In this talk, I will show how molecular modeling helps in understanding complex systems and deciphering biochemistry information that it is impossible to obtain by experiments. And since the precision of biomolecular modeling results is significantly based on force field (FF) parameters, the importance of developing FFs will be demonstrated in this talk. Force Field development. Our simulation results on the basis of CHARMM36 (C36) FF show that the structures of two aromatic amino acids, Tryptophan (Trp) and Tyrosine (Tyr), deviate from planarity. Hence, we investigated the geometry, dynamics, and out-of-plane vibrations of atoms in these rings by imposing improper torsion and changing torsion angle force constants. To that end, molecular dynamics (MD) simulation and all-atom normal mode analysis (NMA) were implemented. We could match the pattern and frequencies of out-of-plane vibrations of these rings with Raman and infrared spectra, and decrease the extent of out-of-plane vibrations for atoms in these rings. A Helical Peptide in water. AMPs usually have a helical structure on the membrane of bacteria. Some studies have stated that the flexible loop at the middle of helical AMPs, which leads peptide to bend and snap the lipid bilayer, has a direct effect on AMPs activity against bacteria. We computationally studied dynamics and vibrations of a helical and a helix-hinged-helix structure of a LM7-2 in solution. Although some vibrational experimental studies have been done on proteins or peptides, we show extended and interesting details about peptide vibrations by our study. We applied instantaneous NMA and Fourier Transform method to understand how a change in the structure of a peptide will affect peptide fluctuations. Raman and infrared spectra cannot indicate these motions that correspond to the low intensity measured frequencies. A complex lipid membrane. Lipid bilayers play a crucial role in a peptide-membrane interactions. Therefore, more real system of lipids will provide more detail of this interaction. To that end, we have designed the most realistic S. aureus membrane by including 19 different types of lipids, compared to other simulations that implemented a range of 2-5 different lipids. We applied Reverse Monte Carlo method to match lipid bilayer composition to experimental results in the literature. Dynamics and membrane characteristics of this complex system were studied

A Technical Note on Least Squares Mascon Fitting to GRACE Satellite Data to Estimate Total Water Storage Changes in the Middle East

acceptedVersio

Estimation of Groundwater Depletion in Iran’s Catchments Using Well Data

publishedVersio

Story of Man’s Creation for Shelley’s Frankenstein:

This study is an attempt to examine ecofeminism in the patriarchal society of Frankenstein of Shelley. At first glance, the novel is a manifestation of the patriarchal world of Shelley because the male characters are present, and almost all of the women in the novel either kill or die. But it can be perceived that Shelley’s female characters are present in their own ways because they are present in nature, as a matter of fact, the female character’s absence and passivity are the emblems of their overwhelming presence so much that even the monster also has some feminine features, and he is used to being passive, because when he appears, it is either dark or moonlight, both of them have feminine attributes. The narrations of novel events are almost described in the sea, which is also the female symbol. Hence, Shelley tries to increase the women’s presence in her own ways in her novel through natural features. The presentation of natural elements influences Monster so much that he also reveals the feminine, goddess features. It can be concluded that the research method of this study is to find Shelley’s ecofeminism attributes, the actual presence of women, and their virtual absence due to ecofeminism, because Shelley has used their own specific ways to show that women are very present in her patriarchal society so much that even all of the male characters have dual features and the feminine features are not absent but they are very present in nature and characters of the novel. Therefore, women’s absence is Shelley’s method to reveal their absolute presence

Planarity and out-of-plane vibrational modes of tryptophan and tyrosine in biomolecular modeling

Tryptophan and tyrosine are aromatic amino acids that play significant roles in the folding processes of proteins at water-membrane interfaces because of their amphipathic structures. Employing appropriate heteroaromatic molecular structures are essential for obtaining accurate dynamics and predictive capabilities in molecular simulations of these amino acids. In this study, molecular dynamics simulations that applied the most recent version of the CHARMM36 force field were conducted on aqueous solutions of tryptophan and of tyrosine. Geometric analysis and dynamics quantified how aromatic rings deviated from planar structures and exhibited out-of-plane fluctuations. Radial distribution functions showed possible biological significance because extent of ring planarity slightly affected local water concentrations near aromatic rings. Instantaneous all-atom normal mode analysis (NMA) and Fourier transformation of time autocorrelation functions of out-of-plane displacements were applied to study out-of-plane vibrations of atoms in those rings. NMA started with minimum energy configurations and then averaged over fluctuations in aqueous solution. The frequencies and frequency patterns that were obtained for tryptophan and tyrosine with CHARMM36 differed from literature reports of Raman spectra, infrared spectra, and frequencies calculated using quantum mechanics, with some out-of-plane modes found at higher frequencies. Effects of imposing improper torsion potentials and changing torsion angle force constants were investigated for all atoms in the rings of tryptophan and tyrosine. Results show that these coarse force fields variations only affect planarity and out-of-plane vibrations of atoms within the rings, not other vibrations. Although increasing improper torsion force constants reduced deviations from aromatic ring planarity significantly, it increased out-of-plane mode frequencies. Reducing torsion angle force constants (with and without improper torsions) shifted modes to lower frequencies. A combination of decreasing most torsion angle force constants for ring atoms in both amino acids and including improper torsion forces attained frequencies and frequency patterns for out-of-plane normal modes that were more similar to literature spectra. These force field variations decreased the extents of out-of-plane vibrations within the heteroaromatic rings of tryptophan, especially around the nitrogen atom in the ring, but not within the heteroaromatic ring of tyrosine. Conclusions were unaffected by peptide endgroup, water, or simulation ensemble

Computing Individual Area per Head Group Reveals Lipid Bilayer Dynamics

Lipid bilayers express a range of phases from solid-like to gel-like to liquid-like as a function of temperature and lipid surface concentration. The area occupied per lipid head group serves as one useful indicator of the bilayer phase, in conjunction with the two-dimensional radial distribution function (i.e., structure factor) within the bilayer. Typically, the area per head group is determined by dividing the bilayer area equally among all head groups. Such an approach is less satisfactory for a multicomponent set of diverse lipids. In this work, area determination is performed on a lipid-by-lipid basis by attributing to a lipid the volume that surrounds each atom. Voronoi tessellation provides this division of the interfacial region on a per-atom basis. The method is applied to a multicomponent system of water, NaCl, and 19 phospholipid types that was devised recently [Langmuir 2022, 38, 9481–9499] as a computational representation of the Gram-positive Staphylococcus aureus phospholipid bilayer. Results demonstrate that lipids and water molecules occupy similar extents of area within the interfacial region; ascribing area only to head groups implicitly incorporates assumptions about head group hydration. Results further show that lipid tails provide non-negligible contributions to area on the membrane side of the bilayer–water interface. Results for minimum and maximum area of individual lipids reveal that spontaneous fluctuations displace head groups more than 10 Å from the interfacial region during an NPT simulation at 310 K, leading to a zero contribution to total area at some times. Total area fluctuations and fluctuations per individual lipid relax with a correlation time of ∼10 ns. The method complements density profile as an approach to quantify the structure and dynamics of computational lipid bilayers

The Collapse of Heterosexism and Phallogocentrism in Caryl Churchill’s Cloud Nine

Caryl Churchill (1938- ) is one of the most illustrious contemporary British playwrights whose theatrical productions are world-widely acclaimed. Churchill’s theatrical innovations, her explorations with new forms, her double commitment to the causes of both socialism and feminism are among the reasons for which Churchill has been transatlantically awarded and acclaimed. In Cloud Nine (1978), that is going to be dealt with in the present study, what is intended to be undertaken is the analysis of the play on the basis of the Butlerian key concept of gender performativity in order to designate Caryl Churchill’s anti-heterosexist and anti-phallogocentric outlook. According to Judith Butler, who is regarded to be an eminent poststructuralist theorist, gender identity is not an interior essence of the subject. By considering gender as something fabricated, and thus performative, Butler calls into question the basis of Western civilization, which is totally phallogocentric and heterosexist. Butler’s performativity of gender identity, which reveals the baselessness of whatever Western Civilizaion centers on, is also something we can perceive in Churchill’s Cloud Nine.Key words: Caryl Churchill; Judith Butler; Gender identity; Gender performativity; Phallogocentrism; Heterosexism; Binary opposition

Effects of ethanolic extract of Artemisia persica on scopolamine-induced cognitive impairment and anxiety in rats

Background: Artemisia persica is used as an antiseptic, carminative, appetizer, antiparasitic, and antipyretic agent as well as to relieve fascial pains, and in the past, was used to relieve neuropathic pain and facilitate uterine contractions during childbirth. Objective: The aim of this study was to investigate the antioxidant potential and effects of A. persica on scopolamine-induced cognitive impairments and anxiety. Methods: In this experimental study, 50 male rats were randomly divided into 5 groups of 10 each, including control group, scopolamine (0.7 mg/kg, intraperitoneal injection) group, and three groups receiving scopolamine and ethanolic Artemisia persica extract (100, 200, and 400 mg/kg). After three weeks of treatment, behavioral tests including passive avoidance memory, plus maze test, and rotarod test were conducted. The level of malondialdehyde and the antioxidant capacity of the serum and brain in the rats were measured. Results: Treatment with A. persica extract at 100, 200, and 400 mg/kg in rats receiving scopolamine caused a significant increase in secondary latency in shuttle Box test (P < 0.01). Treatment of rats receiving scopolamine with A. persica extract at 100, 200, and 400 mg/kg significantly decreased the time elapsed in closed arms and significantly increased the time elapsed in the open arms in plus maze test (P < 0.05). Conclusion: The results of this study indicate that A. persica can act as a potent neuropharmacologic agent against cognitive impairment by modulating cholinergic activity and neuritis in the rat hippocampu