The mechanical properties of a single titin immunoglobulin-like domain (I27) are studied, based on the virial stress definition, via STEERED MOLECULAR DYNAMICS simulation. Moreover, the effects of biological conditions on the obtained results are investigated. Due to different viewpoints on virial stress definition, the role of kinetic stress in virial stress definition is elucidated. The obtained Young's modulus is about 0.7±0.1 GPa. It is found that the ultimate stress decreases nonlinearly and the Young's modulus decreases almost linearly with an increase in temperature. It is observed that the mechanical properties decrease with a decrease in the strain rate. The mechanical properties are not sensitive to small unfolding forces, but they rise up with an increase in the force magnitude afterwards. Considering the kinetic stress term in calculation of virial stress increases the accuracy of the results, but does not have a significant effect on mechanical properties, especially at low temperatures. This implies that the kinetic stress term can be ignored at low temperatures. This study furnishes a basis for the I27 domain, where mechanical properties must be taken into account.

In recent times, due to the rapid development of biological systems, the analysis and study of biological systems has become a hot topic. One of the most fundamental aspects of the study of these systems is the analysis of mechanical properties. In this article, the analysis of the bending behavior of the DNA origami cantilever beam has been investigated. The analysis of this behavior has been done using two important methods, STEERED MOLECULAR DYNAMICS simulation and nonlinear theory. First, a model of a DNA origami beam is designed and modeled. Then, two different methods have been used to check the changes in the deflection in this beam. In the first method, the STEERED MOLECULAR DYNAMICS simulation is used and the changes in deflection are evaluated. In the second method, by analyzing the nonlinear theory, the relationships related to large deformations in the DNA origami beam have been obtained. Finally, the variation of the deflection for this mode has also been specified using nonlinear theoretical relations. This article shows that the results of the two methods have a very good Validation, as a result, the use of the nonlinear theory method can be effective in the study of MOLECULAR DYNAMICS in order to reduce computational and laboratory costs in the mechanical analysis of biological materials. Also, the nonlinear theory method can be of great importance for investigating the mechanical properties of biological systems for innovation in research related to the design and construction of these types of systems.

The fatal SARS-COV-2 virus appeared in China at the end of 2019 for the first time. This virus has similar sequence with SARS-COV in 2002, but its infection is very high rate. On the other hand, SARS-COV-2 is a RNA virus and requires RNA-dependent RNA polymerase (RdRp) to transcribe its viral genome. Due to the availability of the active site of this enzyme, an effective treatment is targeting it to inhibit SARS-COV-2 reproduction. Remdesivir is an inhibitor for Hepatitis C and Ebola that is approved by Food and Drug Administration. Also, it has shown good results in inhibition of main protease and RdRp enzyme of SARS-COV-2. In this paper, the inhibitory of Remdesivir in various temperatures has been observed using STEERED MOLECULAR DYNAMICS simulation. For this reason, the binding affinity of Remdesivir and RdRp were evaluated by MOLECULAR docking at four different temperatures (from 17 to 47 ° C). According to the results, the rupture force and pulling work to separate the Remdesivir from RdRp decrease with increasing temperature. It is also shown that at higher temperatures, Gibbs free energy is reduced due to its relation with pulling work.

This paper deals with atomistic modeling of nanomechanical behavior of actin monomer. The majorcytoskeletal protein of most cells is actin, which is responsible for the mechanical properties of the cells.Actin also plays critical mechanical roles in many cellular processes which give structural support tocells and links the interior of the cell with its surroundings. Based on the accuracy of atomistic-basedmethods such as MOLECULAR DYNAMICS simulations, in this paper, we perform a series of STEEREDMOLECULAR DYNAMICS simulations on both ATP and ADP single actin monomers to determine theirintrinsic MOLECULAR strength. The effect of virtual spring of STEERED MOLECULAR DYNAMICS on themechanical behavior of actin monomer is investigated. The results reveal increasing the virtual springconstant leads to convergence of the stiffness. The stiffness of ADP actin and ATP actin is calculated as215.16 and 228.24 pN/Å, respectively. The results also show higher stiffness and Young’s modulus forATP G-actin in comparison to ADP G-actin. In order to compare the behavior of ATP and ADP Gactins, the number of hydrogen bonds and nonbonded energies between the nucleotide and the proteinare analyzed. The obtained persistent length is 15.61 mm which is in good agreement with the otherreported literature values.

With the increasing development of the pharmaceutical industry and producing drugs with specific performance, its transfer into cells is also of great importance. Cell membranes are effectively impermeable to hydrophilic compounds unless the permeation is facilitated by dedicated transport systems. As a consequence, there is much interest finding ways to facilitate the transport of molecules across cell membranes. Cell-penetrating peptides (CPPs) in particular have shown much promise as potential delivery agents. That have been claimed to penetrate cell membranes in an energy- and receptor-independent manner. In the present investigation, the translocation of PENETRATIN into the cell membrane is carried out applying constant velocity STEERED MOLECULAR DYNAMICS via MARTINI coarse grain approach. In order to study the orientation of peptide as it get closer to the membrane, equilibrium simulation is carried out and it is shown that to investigate the penetration process, STEERED MOLECULAR DYNAMICS simulation must be applied.  Energy barrier upon the insertion is calculated and its diffusion in the membrane is considered. It is shown that pore formation phenomenon breaks down the energy barrier and facilitates the translocation process which is in agreement with previous researches. Furthermore, 110 kJ/mol energy barrier is obtained from simulations for this peptide.

Scorpion venom is a rich source of toxins which have great potential to develop new therapeutic agents. Scorpion chloride channel toxins (ClTxs), such as Chlorotoxin selectively inhibit human Matrix Methaloproteinase-2 (hMMP-2). The inhibitors of hMMP-2 have potential use in cancer therapy. Three new ClTxs, meuCl14, meuCl15 and meuCl16, derived from the venom transcriptome of Iranian scorpion, M. eupeus (Buthidea family), show high sequence identity (71. 4%) with Chlorotoxin. Here, 3-D homology model of new ClTxs were constructed. The models were optimized by MOLECULAR DYNAMICS simulation based on MDFF (MOLECULAR DYNAMICS flexible fitting) method. New ClTxs indicate the presence of CSα β folding of other scorpion toxins. A docking followed by STEERED MOLECULAR DYNAMICS (SMD) simulations to investigate the interactions of meuCl14, meuCl15, and meuCl16 with hMMP-2 was applied. The current study creates a correlation between the unbinding force and the inhibition activities of meuCl14, meuCl15 and meuCl16 to shed some insights as to which toxin may be used as a drug deliverer. To this aim, SMD simulations using Constant Force Pulling method were carried out. The SMD provided useful details related to the changes of electrostatic, van de Waals (vdW), and hydrogen-bonding (H-bonding) interactions between ligands and receptor during the pathway of unbinding. According to SMD results, the interaction of hMMP-2 with meuCl14 is more stable. In addition, Arginine residue was found to contribute significantly in interaction of ClTxs with hMMP-2. All in all, the present study is a dynamical approach whose results are capable of being implemented in structure-based drug design.

Titin is the longest protein found in striated skeletal and cardiac muscle myofibrils. This protein with a length of about 1µ m, has multiple domains consisting of PEVK region (proline, glutamic acid, valine, and lysine residues), and immunoglobulin-like (Ig) and fibronectin domains. In muscles, titin owns unique elastic properties in the I-band region and it is responsible for restoration of muscle to its slack length during the passive contractions. I27 (27 th immunoglobulin domain) is one of the important regions of titin which has been studied extensively by researchers. An important feature of this region is the connection with calcium ion which charges the region and causes pH to change. In this paper the unfolding force of I27 domain has been investigated by considering various pHs in three states of neutral, acidic and basic, using STEERED MOLECULAR dynamic simulations. The results showed that unfolding stiffness of I27 domain depends significantly on pH changes. It decreases by increasing or decreasing pH value and getting away from the neutral state. In the neutral state the highest value of force is needed to break the hydrogen bonds and start the unfolding process. According to the results, titin’ s performance can be improved by changing pH. This proves useful in cases where titin is stiffer than usual or there is a malfunction in the unfolding process.