Manifold optimization methods for macromolecular docking

Thesis (Ph.D.)--Boston UniversityThis thesis develops efficient algorithms for local optimization problems encountered in predictive docking of biological macromolecules. Predictive docking, defined as computationally obtaining a model of the bound complex from the coordinates of the two component molecules, is one of the fundamental and challenging problems in computational structural biology. Docking methods generally search for the minima of an energy or scoring function that estimates the binding free energy or, more frequently, the interaction energy, of the two molecules. These energy functions generally have large numbers of local minima, resulting in extremely rugged energy landscapes. Therefore, independently of the algorithm used for sampling the conformational space, virtually all docking algorithms include some type of local continuous minimization of the energy function. Most state-of-the-art algorithms allow for the free movement of all atoms of the two molecules and rely on the minimization of the energy function to enforce structural constraints of the molecules. In contrast this thesis exploits the partial or complete rigidity of the molecules when defining the conformational space. As a result, the local optimization problems are formulated as optimization problems on appropriately defined manifolds. In the case of rigid docking, a novel manifold representation of rigid motions of a body is introduced that resolves many of the optimization difficulties associated with the commonly used manifold for this purposed , the so-called Special Euclidean group, SE(3). These difficulties arise from a coupling that SE(3) introduces between the rotational and translational move of the body. The new representation decouples these moves and results in a more appropriate and flexible optimization algorithm. Experimental results show that the proposed algorithm is an order of magnitude more efficient than the current state-of-the-art algorithms. The proposed manifold optimization approach is then extended to the case of flexible docking. The novel manifold representation of rigid motions is combined with the so-called internal coordinate representation of flexible moves to define a new manifold to which the original manifold optimization algorithm can be directly extended. Computational results show that the resulting optimization algorithm is substantially more efficient than energy minimization using a traditional all-atom optimization algorithm while producing solutions of comparable quality. It is shown that the application of the proposed local optimization algorithm as one of the components of a multi-stage refinement protocol for protein-protein docking contributes significantly to the refinement stage by helping to move the distribution of docking decoys closer to the corresponding bound structures. Finally, it is shown that the approach of the thesis can be substantially generalized to address the problem of minimization of a cost function that depends on the location and poses of one or more rigid bodies, or bodies that consist of rigid parts hinged together. This is a formulation used in a number of engineering applications other than molecular docking

Interactions of Colorectal Cancer, Dietary Fats, and Polymorphisms of Arachidonate Lipoxygenase and Cyclooxygenase Genes: A Literature Review

ObjectiveGenetics and dietary factors play important roles in the development of colorectal cancer (CRC). However, the underlying mechanisms of the interactions between CRC, gene polymorphisms, and dietary fat are unclear. This review study investigated the effects of polymorphisms of arachidonate lipoxygenase (ALOX) and cyclooxygenase (COX) genes in the association between CRC and dietary fat.MethodsAll the related papers published from 2000 to 2022 were collected from different databases such as PubMed, Science Direct, Scopus, and Cochran using related keywords such as colorectal cancer, ALOX, COX, polymorphism, and dietary fat. Non-English and unrelated documents were excluded.ResultsSome single-nucleotide polymorphisms (SNPs) in the ALOX and COX genes, such as rs2228065, rs6413416, and rs4986832 in the ALOX gene, and rs689465 in the COX gene may play significant roles in the association between the risk of CRC and dietary fats. SNPs of ALOX and COX genes may influence the effects of dietary fatty acids on the risk of CRC.ConclusionSome polymorphisms of the ALOX and COX genes may have important roles in the effects of dietary fat on the risk of CRC. If future studies confirm these results, dietary recommendations for preventing colorectal cancer may be personalized based on the genotype of the ALOX and COX genes

Integrating ARCS motivational model and flipped teaching in L2 classrooms: a case of EFL expository writing

The Attention, Relevance, Confidence, and Satisfaction (ARCS) model provides a basis for integrating motivational dynamics and technological affordances into the design and implementation of instructions to maintain learner motivation and interest. Little attention has been paid to this potential in teaching the complex and often demotivating skill of second/foreign-language (L2) writing. This study examined synergistic effects of ARCS-flipped teaching on Iranian English-as-a-foreignlanguage (EFL) learners’ expository-writing performance and motivation. Participants were 59 EFL learners in two intact classes who were assigned to two groups. In the experimental group, the ARCS model was integrated into the flipped writing course. Hybrid Edmodo plus face-to-face learning spaces were used to implement ARCS strategies alongside the instruction. In the control setting, the model was implemented in the face-to-face writing course. A data-triangulation approach, comprising writing tasks, the Course Interest Survey, and semi structured interviews was adopted. ANCOVA results showed that the ARCS-flipped group outperformed the face-to-face group in their writing performance. Furthermore, the motivational-technological synergy led to more increased learner motivation. Learners’ retrospective perceptions revealed that the flipped features of flexibility, learner-centeredness, relaxed environment, interactivity seamlessness, and collaboration appealed to the learners’ varied time-space preferences, which, in turn, stimulated their motivation, learning engagement, and writing performance

Assessing the recreational value of Dareh Si Castle Park in Arasbaran forests using Contingent Valuation Method (CVM)

Dareh Si is a forested valley located 3 km from southwest of Kalaybar county within the Arasbaran forests in the north of East Azerbayijan Province. High Biodiversity and ecological conditions that generally govern Arasbaran area had turned those forests to a unique biogeographic area of Iran. In this study, the recreational value of the Dareh Si Castle Park (as the minimum recreational value of Arasbaran forests) was estimated using Contingent Valuation Method (CVM). Questionnaires were used to collect the required information. Descriptive statistics of variables were introduced, followed by providing results of LOGIT models and expected WTP values. Analytical results indicated that for each visit to the park the visitors would like to pay 3908 IRR. Annually, 275000 individuals visit the park, which results in the estimated recreational value of 1.074 billion IRR when multiplied by the WTP (The base year was 2007). This was updated based on Consumer Price Indexes (CPI) announced by Central Bank of Islamic Republic of Iran in 2014, accounting for 4.14 billion IRR

Effect of a School-based Nutrition Education Program on the Nutritional Status of Primary School Children

Background and Objectives: Regarding the high prevalence of unhealthy food habits among Iranian children, we aimed to assess the effect of a school-based nutrition education program on nutritional status of primary school students in Shiraz. Materials and Methods: This randomized educational controlled trial was carried out on 221 primary school age children selected by cluster sampling in the elementary schools of Shiraz-Iran. The intervention consisted of 6 nutrition education sessions carried out through one year for children, using active learning methods. Mothers’ education was carried out in person in both lecture and question-answer sessions also via sending text messages and pamphlets. Weight, height and waist circumference (WC) of children were measured before and after the intervention. Also a 168-item food frequency questionnaire was completed. Two separate nutrition knowledge questionnaires were filled up by children and their mothers. Data were analyzed using SPSS version 16. Results: 171 children (83 in the case and 88 in the control group), aged 9.5-10.5 years, completed the study. Anthropometric and nutritional knowledge of the participants in both the intervention and control groups was significantly increased. Weight, height, WC and nutritional knowledge increased significantly more in the intervention group compared to the controls. Consumption of fruits and vegetables decreased in the intervention group while plain sugar and fast foods intake increased among the controls. There were no significant differences between the changes in the intake of any of the food groups in the two groups. Conclusions: In conclusion, the designed nutrition education program could increase students’ nutritional knowledge, and lead to a non-significant change towards reducing the consumption of unhealthy foods such as fast foods, sweets and salty snacks

The Impact of Side-Chain Packing on Protein Docking Refinement

We study the impact of optimizing the side-chain positions in the interface region between two proteins during the process of binding. Mathematically, the problem is similar to side-chain prediction, which has been extensively explored in the process of protein structure prediction. The protein–protein docking application, however, has a number of characteristics that necessitate different algorithmic and implementation choices. In this work, we implement a distributed approximate algorithm that can be implemented on multiprocessor architectures and enables a trade-off between accuracy and running speed. We report computational results on benchmarks of enzyme–inhibitor and other types of complexes, establishing that the side-chain flexibility our algorithm introduces substantially improves the performance of docking protocols. Furthermore, we establish that the inclusion of unbound side-chain conformers in the side-chain positioning problem is critical in these performance improvements. The code is available to the community under open source license