Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 14

Search results for: Y. Shimizu

14 Analyzing Students’ Preferences for Academic Advising: Cases of Two Institutions in Greater Tokyo in Japan

Authors: Megumi Yamasaki, Eiko Shimizu

Abstract:

The term academic advisor system first appeared in 2012 in Japan. After ten years, it is not yet functioning. One of Japanese college students’ characteristics is that they choose an institution but may not be interested in a major and want to earn a degree for a career. When the university encourages students to develop competencies as well as students to set personal goals during college life, it is critical to support students develop self-directed attitudes and advocacy skills. This paper will analyze the students’ current stage and how academic advising supports their development.

Keywords: academic advising, student development, self-directed, self-advocacy

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13 Model Predictive Control Using Thermal Inputs for Crystal Growth Dynamics

Authors: Takashi Shimizu, Tomoaki Hashimoto

Abstract:

Recently, crystal growth technologies have made progress by the requirement for the high quality of crystal materials. To control the crystal growth dynamics actively by external forces is useuful for reducing composition non-uniformity. In this study, a control method based on model predictive control using thermal inputs is proposed for crystal growth dynamics of semiconductor materials. The control system of crystal growth dynamics considered here is governed by the continuity, momentum, energy, and mass transport equations. To establish the control method for such thermal fluid systems, we adopt model predictive control known as a kind of optimal feedback control in which the control performance over a finite future is optimized with a performance index that has a moving initial time and terminal time. The objective of this study is to establish a model predictive control method for crystal growth dynamics of semiconductor materials.

Keywords: model predictive control, optimal control, process control, crystal growth

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12 Prediction of Malawi Rainfall from Global Sea Surface Temperature Using a Simple Multiple Regression Model

Authors: Chisomo Patrick Kumbuyo, Katsuyuki Shimizu, Hiroshi Yasuda, Yoshinobu Kitamura

Abstract:

This study deals with a way of predicting Malawi rainfall from global sea surface temperature (SST) using a simple multiple regression model. Monthly rainfall data from nine stations in Malawi grouped into two zones on the basis of inter-station rainfall correlations were used in the study. Zone 1 consisted of Karonga and Nkhatabay stations, located in northern Malawi; and Zone 2 consisted of Bolero, located in northern Malawi; Kasungu, Dedza, Salima, located in central Malawi; Mangochi, Makoka and Ngabu stations located in southern Malawi. Links between Malawi rainfall and SST based on statistical correlations were evaluated and significant results selected as predictors for the regression models. The predictors for Zone 1 model were identified from the Atlantic, Indian and Pacific oceans while those for Zone 2 were identified from the Pacific Ocean. The correlation between the fit of predicted and observed rainfall values of the models were satisfactory with r=0.81 and 0.54 for Zone 1 and 2 respectively (significant at less than 99.99%). The results of the models are in agreement with other findings that suggest that SST anomalies in the Atlantic, Indian and Pacific oceans have an influence on the rainfall patterns of Southern Africa.

Keywords: Malawi rainfall, forecast model, predictors, SST

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11 Model Predictive Control with Unscented Kalman Filter for Nonlinear Implicit Systems

Authors: Takashi Shimizu, Tomoaki Hashimoto

Abstract:

A class of implicit systems is known as a more generalized class of systems than a class of explicit systems. To establish a control method for such a generalized class of systems, we adopt model predictive control method which is a kind of optimal feedback control with a performance index that has a moving initial time and terminal time. However, model predictive control method is inapplicable to systems whose all state variables are not exactly known. In other words, model predictive control method is inapplicable to systems with limited measurable states. In fact, it is usual that the state variables of systems are measured through outputs, hence, only limited parts of them can be used directly. It is also usual that output signals are disturbed by process and sensor noises. Hence, it is important to establish a state estimation method for nonlinear implicit systems with taking the process noise and sensor noise into consideration. To this purpose, we apply the model predictive control method and unscented Kalman filter for solving the optimization and estimation problems of nonlinear implicit systems, respectively. The objective of this study is to establish a model predictive control with unscented Kalman filter for nonlinear implicit systems.

Keywords: optimal control, nonlinear systems, state estimation, Kalman filter

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10 Health Promotion Programs for Fifteen Years Decreased Loneliness and Increased Happiness for Elementary School Children in Yuzawa Town, Japan

Authors: Takeo Shibata, Arihito Endo, Chika Hiraga, Akemi Kunimatsu, Yoko Shimizu

Abstract:

Introduction: A health promotion program, Yuzawa family health plan, was initiated in 2002. It has been held for fifteen years. Yuzawa Town is famous with hot springs and ski resorts. We evaluated the changes in mental status in elementary school children. Methods: questionnaires survey had been held every five years. 196 questionnaires were corrected (94 boys and 102 girls). Changes for their anxieties, loneliness, confiding, problem-solving, risk breaching, communications, happiness, and life satisfaction were evaluated by chi-square test. Results: The rate of loneliness and life dissatisfactions decreased. The rates of happiness, confiding in grandparents, and risk breaching, increased. Especially, happiness rates increased for boys, loneliness rate decreased for girls, confiding in grandparents and risk breaching rate increased for girls. Conclusion: Our health promotion programs could increase mental health status in elementary school children.

Keywords: health promotion, mental status, elementary school, loneliness, happiness

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9 State Estimation Based on Unscented Kalman Filter for Burgers’ Equation

Authors: Takashi Shimizu, Tomoaki Hashimoto

Abstract:

Controlling the flow of fluids is a challenging problem that arises in many fields. Burgers’ equation is a fundamental equation for several flow phenomena such as traffic, shock waves, and turbulence. The optimal feedback control method, so-called model predictive control, has been proposed for Burgers’ equation. However, the model predictive control method is inapplicable to systems whose all state variables are not exactly known. In practical point of view, it is unusual that all the state variables of systems are exactly known, because the state variables of systems are measured through output sensors and limited parts of them can be only available. In fact, it is usual that flow velocities of fluid systems cannot be measured for all spatial domains. Hence, any practical feedback controller for fluid systems must incorporate some type of state estimator. To apply the model predictive control to the fluid systems described by Burgers’ equation, it is needed to establish a state estimation method for Burgers’ equation with limited measurable state variables. To this purpose, we apply unscented Kalman filter for estimating the state variables of fluid systems described by Burgers’ equation. The objective of this study is to establish a state estimation method based on unscented Kalman filter for Burgers’ equation. The effectiveness of the proposed method is verified by numerical simulations.

Keywords: observer systems, unscented Kalman filter, nonlinear systems, Burgers' equation

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8 Analyzing Habits of Brushing Teeth in Yuzawa Town, Japan

Authors: Takeo Shibata, Arihito Endo, Akemi Kunimatsu, Chika Hiraga, Yoko Shimizu

Abstract:

Introduction: Yuzawa Town, located in the Niigata prefecture of Japan, is famous for its hot springs. A health promotion program, Yuzawa family health plan, was initiated in 2002. It has been held for fifteen years. We evaluated the profiles of brushing teeth in adults. Subjects: 368 questionnaires were corrected from people who live in Yuzawa town. The range of age was between nineteen and sixty-four years old. Methods: Mann-Whitney’s U test and Kruskal-Wallis test were used to evaluate significant differences in frequencies of brushing teeth per a day. Chi-square test and the adjusted residuals were used to evaluate when they brush their teeth. Results: Women showed greater frequencies of brushing teeth per a day than men. No difference was shown by age. Construction workers showed fewer frequencies of brushing teeth. Specialized technicians, clerical workers, and housewives showed greater frequencies. People who know Yuzawa family health plan, take a regular life, or take a breakfast every day showed greater frequencies. People who think not healthy, don’t care a balance of foods, don’t take yearly health check-up, or smoke showed fewer frequencies. After breakfast, women and specialized technicians showed greater frequencies, and construction workers and self-employed workers showed fewer frequencies. After lunch, clerical workers and specialized technicians showed greater frequencies. There was no significant difference at after waking up, after dinner, and before going to bed. Construction workers showed a lower rate of having a marital partner and having information of health. Conclusion: Gender and occupational differences were shown in frequencies of brushing teeth per a day. A promotion of teeth brushing for male, especially construction workers and self-employed workers, is needed.

Keywords: health promotion, Yuzawa family health plan, brushing teeth, occupational difference

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7 Effect of Retention Time on Kitchen Wastewater Treatment Using Mixed Algal-Bacterial Consortia

Authors: Keerthi Katam, Abhinav B. Tirunaghari, Vinod Vadithya, Toshiyuki Shimizu, Satoshi Soda, Debraj Bhattacharyya

Abstract:

Researchers worldwide are increasingly focusing on the removal of carbon and nutrient from wastewater using algal-bacterial hybrid systems. Algae produce oxygen during photosynthesis, which is taken up by heterotrophic bacteria for mineralizing organic carbon to carbon dioxide. This phenomenon reduces the net mechanical aeration requirement of aerobic biological wastewater treatment processes. Consequently, the treatment cost is also reduced. Microalgae also participate in the treatment process by taking up nutrient (N, P) from wastewater. Algal biomass, if harvested, can generate value-added by-products. The aim of the present study was to compare the performance of two systems - System A (mixed microalgae and bacteria) and System B (diatoms and bacteria) in treating kitchen wastewater (KWW). The test reactors were operated at five different solid retention times (SRTs) -2, 4, 6, 8, and 10-days in draw-and-fill mode. The KWW was collected daily from the dining hall-kitchen area of the Indian Institute of Technology Hyderabad. The influent and effluent samples were analyzed for total organic carbon (TOC), total nitrogen (TN) using TOC-L analyzer. A colorimetric method was used to analyze anionic surfactant. Phosphorus (P) and chlorophyll were measured by following standard methods. The TOC, TN, and P of KWW were in the range of 113.5 to 740 mg/L, 2 to 22.8 mg/L, and 1 to 4.5 mg/L, respectively. Both the systems gave similar results with 85% of TOC removal and 60% of TN removal at 10-d SRT. However, the anionic surfactant removal in System A was 99% and 60% in System B. The chlorophyll concentration increased with an increase in SRT in both the systems. At 2-d SRT, no chlorophyll was observed in System B, whereas 0.5 mg/L was observed in System A. At 10-d SRT, the chlorophyll concentration in System A was 7.5 mg/L, whereas it was 4.5 mg/L in System B. Although both the systems showed similar performance in treatment, the increase in chlorophyll concentration suggests that System A demonstrated a better algal-bacterial symbiotic relationship in treating KWW than System B.

Keywords: diatoms, microalgae, retention time, wastewater treatment

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6 Effects of Lateness Gene on Yield and Related Traits in Indica Rice

Authors: B. B. Rana, M. Yokota, Y. Shimizu, Y. Koide, I. Takamure, T. Kawano, M. Murai

Abstract:

Various genes which control or affect heading time have been found in rice. Out of them, Se1 and E1 loci play important roles in determining heading time by controlling photosensitivity. An isogenic-line pair of late and early lines were developed from progenies of the F1 from Suweon 258 × 36U. A lateness gene tentatively designated as “Ex” was found to control the difference in heading time between the early and late lines mentioned above. The present study was conducted to examine the effect of Ex on yield and related traits. Indica-type variety Suweon 258 was crossed with 36U, which is an Ur1 (Undulate rachis-1) isogenic line of IR36. In the F2 population, comparatively early-heading, late-heading and intermediate-heading plants were segregated. Segregation similar to that by the three types of heading was observed in the F3 and later generations. A late-heading plant and an early-heading plant were selected in the F8 population from an intermediate-heading F7 plant, for developing L and E of the isogenic-line pair, respectively. Experiments for L and E were conducted by randomized block design with three replications. Transplanting was conducted on May 3 at a planting distance of 30 cm × 15 cm with two seedlings per hill to an experimental field of the Faculty of Agriculture, Kochi University. Chemical fertilizers containing N, P2O5 and K2O were applied at the nitrogen levels of 4 g/m2, 9 g/m2 and 18 g/m2 in total being denoted by "N4", "N9" and "N18", respectively. Yield, yield components and other traits were measured. Ex delayed 80%-heading by 17 or 18 days in L as compared with E. In total brown rice yield (g/m2), L was 635, 606 and 590, and E was 577, 548 and 501, respectively, at N18, N9 and N4, indicating that Ex increased this trait by 10% to 18%. Ex increased yield-1.5 mm sieve (g/m2) b 9% to 15% at the three fertilizer levels. Ex increased the spikelet number per panicle by 16% to 22%. As a result, the spikelet number per m2 was increased by 11% to 18% at the three fertilizer levels. Ex decreased 1000-grain weight (g) by 2 to 4%. L was not significantly different from E in ripened-grain percentage, fertilized-spikelet percentage and percentage of ripened grains to fertilized spikelets. Hence, it is inferred that Ex increased yield by increasing spikelet number per panicle. Hence, Ex could be utilized to develop high yielding varieties for warmer districts.

Keywords: heading time, lateness gene, photosensitivity, yield, yield components

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5 Proposed Design of an Optimized Transient Cavity Picosecond Ultraviolet Laser

Authors: Marilou Cadatal-Raduban, Minh Hong Pham, Duong Van Pham, Tu Nguyen Xuan, Mui Viet Luong, Kohei Yamanoi, Toshihiko Shimizu, Nobuhiko Sarukura, Hung Dai Nguyen

Abstract:

There is a great deal of interest in developing all-solid-state tunable ultrashort pulsed lasers emitting in the ultraviolet (UV) region for applications such as micromachining, investigation of charge carrier relaxation in conductors, and probing of ultrafast chemical processes. However, direct short-pulse generation is not as straight forward in solid-state gain media as it is for near-IR tunable solid-state lasers such as Ti:sapphire due to the difficulty of obtaining continuous wave laser operation, which is required for Kerr lens mode-locking schemes utilizing spatial or temporal Kerr type nonlinearity. In this work, the transient cavity method, which was reported to generate ultrashort laser pulses in dye lasers, is extended to a solid-state gain medium. Ce:LiCAF was chosen among the rare-earth-doped fluoride laser crystals emitting in the UV region because of its broad tunability (from 280 to 325 nm) and enough bandwidth to generate 3-fs pulses, sufficiently large effective gain cross section (6.0 x10⁻¹⁸ cm²) favorable for oscillators, and a high saturation fluence (115 mJ/cm²). Numerical simulations are performed to investigate the spectro-temporal evolution of the broadband UV laser emission from Ce:LiCAF, represented as a system of two homogeneous broadened singlet states, by solving the rate equations extended to multiple wavelengths. The goal is to find the appropriate cavity length and Q-factor to achieve the optimal photon cavity decay time and pumping energy for resonator transients that will lead to ps UV laser emission from a Ce:LiCAF crystal pumped by the fourth harmonics (266nm) of a Nd:YAG laser. Results show that a single ps pulse can be generated from a 1-mm, 1 mol% Ce³⁺-doped LiCAF crystal using an output coupler with 10% reflectivity (low-Q) and an oscillator cavity that is 2-mm long (short cavity). This technique can be extended to other fluoride-based solid-state laser gain media.

Keywords: rare-earth-doped fluoride gain medium, transient cavity, ultrashort laser, ultraviolet laser

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4 The Role of Cognitive Control and Social Camouflage Associated with Social Anxiety Autism Spectrum Conditions

Authors: Siqing Guan, Fumiyo Oshima, Eiji Shimizu, Nozomi Tomita, Toru Takahashi, Hiroaki Kumano

Abstract:

Risk factors for social anxiety in autism spectrum conditions involve executive attention, emotion regulation, and thought regulation as processes of cognitive dysregulation. Social camouflaging behaviors as strategies used to mask and/or compensate for autism characteristics during social interactions in autism spectrum conditions have also been emphasized. However, the role of cognitive dysregulation and social camouflaging related to social anxiety in autism spectrum conditions has not been clarified. Whether these factors are specific to social anxiety in autism spectrum conditions or common to social anxiety independent of autism spectrum conditions needs to be clarified. Here, we explored risk factors specific to social anxiety in autism spectrum conditions and general risk factors for social anxiety independent of autism spectrum conditions. From the Japanese participants in early adulthood (age=18~39) of the online survey in Japan, those who exceeded the Japanese version Autism-Spectrum Quotient cutoff (33 points or more )were divided into the autism spectrum conditions group (ASC; N=255, mean age=32.08, SD age=5.16)and those who did not exceed the cutoff were divided into the non-autism spectrum conditions group (Non-ASC; N=255, mean age=31.70, SD age=5.09). Using the Japanese versions of the Social Phobia Scale, the Social Interaction Anxiety Scale, and the Short Fear of Negative Evaluation Scale, a composite score for social anxiety was calculated using a method of principal. We also measured emotional control difficulties using the Difficulties in Emotion Regulation Scale, executive attention using the Effortful Control Scale for Adults, rumination using the Rumination-Reflection Questionnaire, and worry using the Penn State Worry Questionnaire. This study was passed through the review of the Ethics Committee. No conflicts of interest. Multiple regression analysis with forced entry method was used to predict social anxiety in the ASC and non-ASC groups separately, based on executive attention, emotion dysregulation, worry, rumination, and social camouflage. In the ASC group, emotion dysregulation (β=.277, p<.001), worry (β=.162, p<.05), assimilation (β=.308, p<.001) and masking (β=.275, p<.001) were significant predictors of social anxiety (F (7,247) = 45.791, p <.001, R2=.565). In the non-ASC groups,emotion dysregulation (β=.171, p<.05), worry (β=.344,p <.001), assimilation (β=.366,p <.001) and executive attention (β=-.132,p <.05) were significant predictors of social anxiety (F (7,207) =47.333, p <.001, R2=.615).The findings suggest that masking was shown to be a risk factor for social anxiety specific to autism spectrum conditions, while emotion dysregulation, worry, and assimilation were shown to be common risk factors for social anxiety, regardless of autism spectrum conditions. In addition, executive attention is a risk factor for social anxiety without autism spectrum conditions.

Keywords: autism spectrum, cognitive control, social anxiety, social camouflaging

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3 Comparison between Conventional Bacterial and Algal-Bacterial Aerobic Granular Sludge Systems in the Treatment of Saline Wastewater

Authors: Philip Semaha, Zhongfang Lei, Ziwen Zhao, Sen Liu, Zhenya Zhang, Kazuya Shimizu

Abstract:

The increasing generation of saline wastewater through various industrial activities is becoming a global concern for activated sludge (AS) based biological treatment which is widely applied in wastewater treatment plants (WWTPs). As for the AS process, an increase in wastewater salinity has negative impact on its overall performance. The advent of conventional aerobic granular sludge (AGS) or bacterial AGS biotechnology has gained much attention because of its superior performance. The development of algal-bacterial AGS could enhance better nutrients removal, potentially reduce aeration cost through symbiotic algae-bacterial activity, and thus, can also reduce overall treatment cost. Nonetheless, the potential of salt stress to decrease biomass growth, microbial activity and nutrient removal exist. Up to the present, little information is available on saline wastewater treatment by algal-bacterial AGS. To the authors’ best knowledge, a comparison of the two AGS systems has not been done to evaluate nutrients removal capacity in the context of salinity increase. This study sought to figure out the impact of salinity on the algal-bacterial AGS system in comparison to bacterial AGS one, contributing to the application of AGS technology in the real world of saline wastewater treatment. In this study, the salt concentrations tested were 0 g/L, 1 g/L, 5 g/L, 10 g/L and 15 g/L of NaCl with 24-hr artificial illuminance of approximately 97.2 µmol m¯²s¯¹, and mature bacterial and algal-bacterial AGS were used for the operation of two identical sequencing batch reactors (SBRs) with a working volume of 0.9 L each, respectively. The results showed that salinity increase caused no apparent change in the color of bacterial AGS; while for algal-bacterial AGS, its color was progressively changed from green to dark green. A consequent increase in granule diameter and fluffiness was observed in the bacterial AGS reactor with the increase of salinity in comparison to a decrease in algal-bacterial AGS diameter. However, nitrite accumulation peaked from 1.0 mg/L and 0.4 mg/L at 1 g/L NaCl in the bacterial and algal-bacterial AGS systems, respectively to 9.8 mg/L in both systems when NaCl concentration varied from 5 g/L to 15 g/L. Almost no ammonia nitrogen was detected in the effluent except at 10 g/L NaCl concentration, where it averaged 4.2 mg/L and 2.4 mg/L, respectively, in the bacterial and algal-bacterial AGS systems. Nutrients removal in the algal-bacterial system was relatively higher than the bacterial AGS in terms of nitrogen and phosphorus removals. Nonetheless, the nutrient removal rate was almost 50% or lower. Results show that algal-bacterial AGS is more adaptable to salinity increase and could be more suitable for saline wastewater treatment. Optimization of operation conditions for algal-bacterial AGS system would be important to ensure its stably high efficiency in practice.

Keywords: algal-bacterial aerobic granular sludge, bacterial aerobic granular sludge, Nutrients removal, saline wastewater, sequencing batch reactor

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2 Sugar-Induced Stabilization Effect of Protein Structure

Authors: Mitsuhiro Hirai, Satoshi Ajito, Nobutaka Shimizu, Noriyuki Igarashi, Hiroki Iwase, Shinichi Takata

Abstract:

Sugars and polyols are known to be bioprotectants preventing such as protein denaturation and enzyme deactivation and widely used as a nontoxic additive in various industrial and medical products. The mechanism of their protective actions has been explained by specific bindings between biological components and additives, changes in solvent viscosities, and surface tension and free energy changes upon transfer of those components into additive solutions. On the other hand, some organisms having tolerances against extreme environment produce stress proteins and/or accumulate sugars in cells, which is called cryptobiosis. In particular, trehalose has been drawing attention relevant to cryptobiosis under external stress such as high or low temperature, drying, osmotic pressure, and so on. The function of cryptobiosis by trehalose has been explained relevant to the restriction of the intra-and/or-inter-molecular movement by vitrification or from the replacement of water molecule by trehalose. Previous results suggest that the structure and interaction between sugar and water are a key determinant for understanding cryptobiosis. Recently, we have shown direct evidence that the protein hydration (solvation) and structural stability against chemical and thermal denaturation significantly depend on sugar species and glycerol. Sugar and glycerol molecules tend to be preferentially or weakly excluded from the protein surface and preserved the native protein hydration shell. Due to the protective action of the protein hydration shell by those molecules, the protein structure is stabilized against chemical (guanidinium chloride) and thermal denaturation. The protective action depends on sugar species. To understand the above trend and difference in detail, it is essentially important to clarify the characteristics of solutions containing those additives. In this study, by using wide-angle X-ray scattering technique covering a wide spatial region (~3-120 Å), we have clarified structures of sugar solutions with the concentration from 5% w/w to 65% w/w. The sugars measured in the present study were monosaccharides (glucose, fructose, mannose) and disaccharides (sucrose, trehalose, maltose). Due to observed scattering data with a wide spatial resolution, we have succeeded in obtaining information on the internal structure of individual sugar molecules and on the correlation between them. Every sugar gradually shortened the average inter-molecular distance as the concentration increased. The inter-molecular interaction between sugar molecules was essentially showed an exclusive tendency for every sugar, which appeared as the presence of a repulsive correlation hole. This trend was more weakly seen for trehalose compared to other sugars. The intermolecular distance and spread of individual molecule clearly showed the dependence of sugar species. We will discuss the relation between the characteristic of sugar solution and its protective action of biological materials.

Keywords: hydration, protein, sugar, X-ray scattering

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1 Membrane Permeability of Middle Molecules: A Computational Chemistry Approach

Authors: Sundaram Arulmozhiraja, Kanade Shimizu, Yuta Yamamoto, Satoshi Ichikawa, Maenaka Katsumi, Hiroaki Tokiwa

Abstract:

Drug discovery is shifting from small molecule based drugs targeting local active site to middle molecules (MM) targeting large, flat, and groove-shaped binding sites, for example, protein-protein interface because at least half of all targets assumed to be involved in human disease have been classified as “difficult to drug” with traditional small molecules. Hence, MMs such as peptides, natural products, glycans, nucleic acids with various high potent bioactivities become important targets for drug discovery programs in the recent years as they could be used for ‘undruggable” intracellular targets. Cell membrane permeability is one of the key properties of pharmacodynamically active MM drug compounds and so evaluating this property for the potential MMs is crucial. Computational prediction for cell membrane permeability of molecules is very challenging; however, recent advancement in the molecular dynamics simulations help to solve this issue partially. It is expected that MMs with high membrane permeability will enable drug discovery research to expand its borders towards intracellular targets. Further to understand the chemistry behind the permeability of MMs, it is necessary to investigate their conformational changes during the permeation through membrane and for that their interactions with the membrane field should be studied reliably because these interactions involve various non-bonding interactions such as hydrogen bonding, -stacking, charge-transfer, polarization dispersion, and non-classical weak hydrogen bonding. Therefore, parameters-based classical mechanics calculations are hardly sufficient to investigate these interactions rather, quantum mechanical (QM) calculations are essential. Fragment molecular orbital (FMO) method could be used for such purpose as it performs ab initio QM calculations by dividing the system into fragments. The present work is aimed to study the cell permeability of middle molecules using molecular dynamics simulations and FMO-QM calculations. For this purpose, a natural compound syringolin and its analogues were considered in this study. Molecular simulations were performed using NAMD and Gromacs programs with CHARMM force field. FMO calculations were performed using the PAICS program at the correlated Resolution-of-Identity second-order Moller Plesset (RI-MP2) level with the cc-pVDZ basis set. The simulations clearly show that while syringolin could not permeate the membrane, its selected analogues go through the medium in nano second scale. These correlates well with the existing experimental evidences that these syringolin analogues are membrane-permeable compounds. Further analyses indicate that intramolecular -stacking interactions in the syringolin analogues influenced their permeability positively. These intramolecular interactions reduce the polarity of these analogues so that they could permeate the lipophilic cell membrane. Conclusively, the cell membrane permeability of various middle molecules with potent bioactivities is efficiently studied using molecular dynamics simulations. Insight of this behavior is thoroughly investigated using FMO-QM calculations. Results obtained in the present study indicate that non-bonding intramolecular interactions such as hydrogen-bonding and -stacking along with the conformational flexibility of MMs are essential for amicable membrane permeation. These results are interesting and are nice example for this theoretical calculation approach that could be used to study the permeability of other middle molecules. This work was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number 18ae0101047.

Keywords: fragment molecular orbital theory, membrane permeability, middle molecules, molecular dynamics simulation

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